1,2 Diarylbenzimidazoles and their pharmaceutical use

ABSTRACT

Benzimidazoles of general formula I 
                         
and the use of benzimidazole derivatives for the production of pharmaceutical agents for treatment and prophylaxis of diseases that are associated with a microglia activation are described.

This application is a division of copending application U.S. Ser. No.09/759,360, filed Jan. 16, 2001, which claims priority to U.S.Provisional application Ser. 60/178,324, filed Jan. 27, 2000, the entiredisclosures of which are incorporated herein by reference.

Benefit is claimed of the filing date of Jan. 27, 2000 of Provisionalapplication 60/178,324, whose entire disclosure is incorporated byreference herein.

The invention relates to new benzimidazole derivatives and the use ofbenzimidazole derivatives for the production of pharmaceutical agentsfor treatment and prophylaxis of diseases that are associated with amicroglia activation.

Almost all degenerative diseases of the central nervous system areconnected to chronic inflammation. A central step of the inflammationprocess is the activation of mononuclear phagocyte cells, the microglia.This is carried out in, e.g., Alzheimer's disease by senile plaques, inCreutzfeldt-Jacob disease by a prion protein and in ischemic stroke bydead cells. The microglia can remain for a prolonged period in theactivated state, in which they produce and secrete various inflammationfactors, e.g., reactive oxygen/nitrogen intermediate products,proteases, cytokines, complement factors and neurotoxins. The latter inturn produce neuronal dysfunction and degeneration.

For a possible treatment of neuroinflammation, to date non-steroidalantiinflammatory agents (COX II inhibitors) (McGeer, P. L.; Roger,Neurology 42, 447-449 (1992), Rogers, J.; Kirby, L. C.; Hempleman, S.R.; Berry, D. L.; McGeer, P. L.; Kaszniak, A. W.; Zalinski, J.; Cofield,M.; Mansukhani, L.; Wilson, P.; Kogan, F. Neurology 43, 1609-1611(1993), Andersen, K.; Launer, L. J.; Ott, A.; Hoes, A. W.; Breteler, M.M. B.; Hofman, A. Neurology 45, 1441-1445 (1995), Breitner, J. C. S.;Gau, B. A.; Welsh, K. A.; Plassman, B. L.; McDonald, W. M.; Helms, M.J.; Anthony, J. C. Neurology 44, 227-232 (1994), The Canadian Study ofHealth and Aging, Neurology 44, 2073-2079 (1994)), cytokine modulators(McGeer, P. L.; McGeer, E. G. Brain Res. Rev 21:195-218 (1995), McGeer,E. G.; McGeer, P. L., CNS Drugs 7, 214-228 (1997), Barone, F. C. andFeuerstein, G. Z., J. Cerebral Blood Flow and Metabolism 19, 819-834(1999) and complement-cascade-inhibitors (Chen., S.; Frederickson, R. C.A., and Brunden, K. R., Neurobiol. Aging (1996), McGeer, E. G.; McGeer,P. L., Drugs 55: 739-746 (1998)) have been described. These substancesinhibit the synthesis or the action of individual inflammation factors.It would be desirable, however, to have substances that inhibit anearlier step in the inflammation process and thus prevent thedevelopment or action of many inflammation factors.

The problem was solved by preparation of benzimidazole derivatives ofgeneral formula I, their tautomeric or isomeric forms or salts

in which

-   -   R¹ means a monocyclic or bicyclic C₆₋₁₂ aryl group or a        monocyclic or bicyclic 5- to 10-membered heteroaryl group with        1-4 heteroatoms selected from the group that consists of N, S or        O, whereby the mentioned aryl or heteroaryl group can be        substituted with up to three of the following substituents,        independently of one another:        -   F, Cl, Br, I, C(NH)NH₂, C(NH)NHR⁴, C(NH)NR⁴R^(4′),            C(NR⁴)NH₂, C(NR⁴)NHR^(4′), C(NR⁴) NR⁴R^(4′), XOH, XOR⁴,            XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′),            XC(NO(COR⁴))R^(4′) XCN, XCOOH, XCOOR⁴, XCONH₂, XCONR⁴R^(4′),            XCONHR⁴, XCONHOH, XCONHOR⁴, XCOSR⁴ XSR⁴, XSOR⁴, XSO₂R⁴,            SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴, XNR⁴R^(4′),            XNHSO₂R⁴, XN(SO₂R⁴)SO₂R^(4′), XNR⁴SO₂R^(4′), XNHCOR⁴,            XNHCOOR⁴, XNHCONHR⁴, tetrahydro-2,5-dioxopyrrol-1-yl,            2,5-dihydro-2,5-dioxopyrrol-1-yl,            2,7-dihydro-2,7-dioxoisoindol-1-yl, R⁴, whereby two            substituents at R¹, if they are in ortho-position to one            another, can be linked to one another in such a way that            they jointly form methanediylbisoxy, ethane-1,2-diylbisoxy,            propane-1,3-diyl, butane-1,4-diyl,    -   R² means a monocyclic or bicyclic C₆₋₁₀ aryl group or a        monocyclic or bicyclic 5- to 10-membered heteroaryl group with        1-4 heteroatoms selected from the group that consists of N, S or        O, whereby the mentioned aryl or heteroaryl group can be        substituted with up to three of the following substituents,        independently of one another:        -   F, Cl, Br, I, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴,            XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCOOH,            XCOOR⁴, XCONH₂, XCONHR⁴, XCONR⁴R^(4′), XCONHOH, XCONHOR⁴,            XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′),            NO₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XN(SO₂R⁴)SO₂R^(4′),            XNR⁴SO₂R^(4′), tetrahydro-2,5-dioxopyrrol-1-yl,            2,5-dihydro-2,5-dioxopyrrol-1-yl,            2,7-dihydro-2,7-dioxoisoindol-1-yl, R⁴, whereby two            substituents at R², if they are in ortho-position to one            another, can be linked to one another in such a way that            they jointly form methanediylbisoxy, ethane-1,2-diylbisoxy,            propane-1,3-diyl, butane-1,4-diyl,    -   R³ means one or two substituents, which form, independently of        one another:        -   hydrogen, F, Cl, Br, I, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴,            XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′),            XC(NO(COR⁴))R^(4′), XCN, XCOOH, XCOOR⁴, XCONH₂, XCONHR⁴,            XCONR⁴R^(4′), XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴,            XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴,            XNR⁴R^(4′), XNHSO₂R⁴, XNR⁴SO₂R^(4′), XN(SO₂R⁴)(SO₂R⁴),            XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴,            tetrahydro-2,5-dioxopyrrol-1-yl,            2,5-dihydro-2,5-dioxopyrrol-1-yl,            2,7-dihydro-2,7-dioxoisoindol-1-yl, or R³ can be R⁴, whereby            two substituents at R³, if they are in ortho-position to one            another, can be linked to one another in such a way that            they jointly form methanediylbisoxy, ethane-1,2-diylbisoxy,            propane-1,3-diyl, butane-1,4-diyl,    -   R⁴ and R^(4′), independently of one another, mean C₁₋₄        perfluoroalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkinyl, C₃₋₇        cycloalkyl, (C₁₋₃ alkyl-C₃₋₇ cycloalkyl), C₁₋₃ alkyl-C₆₋₁₀ aryl,        C₁₋₃ alkyl-5 to 10-membered heteroaryl; with 1-4 N, S or O        atoms, C₆₋₁₀ aryl or 5- to 10-membered heteroaryl with 1-4 N, S        or O atoms, whereby the aryl and heteroaryl groups can be        substituted with one or two substituents from the group that        consists of F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅, CF₃, C₂F₅ or        else can carry an annelated methanediylbisoxy group or        ethane-1,2-diylbisoxy group, and in addition in a 5-membered        cycloalkyl ring, a ring member can be an N or an O, and in a 6-        or 7-membered cycloalkyl ring, one or two ring members can be N        and/or O, whereby ring nitrogens optionally can be substituted        with C₁₋₃ alkyl or C₁₋₃ alkanoyl,    -   R⁵ and R^(5′), independently of one another, mean C₁₋₆ alkyl,        C₂₋₆ alkenyl, C₂₋₆ alkinyl, whereby a carbon atom can be        exchanged for O, S, SO, SO₂, NH, NC₁₋₃ alkyl or NC₁₋₃ alkanoyl,        C₃₋₇ cycloalkyl-C₀₋₃ alkyl, whereby in a 5-membered cycloalkyl        ring, a ring member can be an N or an O and in a 6- or        7-membered cycloalkyl ring, one or two ring members can be N        and/or O, whereby ring nitrogens optionally can be substituted        with C₁₋₃ alkyl or C₁₋₃ alkanoyl, C₆₋₁₀ aryl or 5- to        10-membered heteroaryl with 1-4 heteroatoms from N, S, and O,        whereby the mentioned alkyl, alkenyl and alkinyl chains can be        substituted with one of the previously mentioned cycloalkyls,        aryls or heteroaryls, whereby all previously mentioned alkyl and        cycloalkyl radicals with up to two substituents consisting of        CF₃, C₂F₅, OH, OC₁₋₃ alkyl, NH2, NHC₁₋₃ alkyl, NHC₁₋₃ alkanoyl,        N(C₁₋₃ alkyl)₂, N(C₁₋₃ alkyl) (C₁₋₃ alkanoyl), COOH, CONH₂,        COOC₁₋₃ alkyl and all previously mentioned aryl and heteroaryl        groups can be substituted with one or two substituents from the        group that consists of F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅,        CF₃, C₂F₅ or else can carry an annelated methanediylbisoxy,        ethane-1,2-diylbisoxy group, or R⁵ and R^(5′) together with the        nitrogen atom form a 5- to 7-membered heterocyclic compound,        which can contain another oxygen, nitrogen or sulfur atom and        can be substituted with C₁₋₄ alkyl, C₁₋₄ alkoxy-C₀₋₂ alkyl, C₁₋₄        alkoxy-carbonyl, aminocarbonyl or phenyl,    -   A means C₁₋₁₀ alkanediyl, C₂₋₁₀ alkenediyl, C₂₋₁₀ alkinediyl,        (C₀₋₅ alkanediyl-C₃₋₇ cycloalkanediyl-C₀₋₅ alkanediyl), whereby        in a 5-membered cycloalkyl ring, a ring member can be an N or an        O, and in a 6- or 7-membered cycloalkyl ring, one or two ring        members can be N and/or O, whereby ring nitrogens optionally can        be substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, whereby in the        above-mentioned aliphatic chains, a carbon atom or two carbon        atoms can be exchanged for O, NH, NC₁₋₃ alkyl, NC₁₋₃ alkanoyl,        and whereby alkyl or cycloalkyl groups can be substituted with        up to two substituents consisting of ═O, OH, OC₁₋₃ alkyl, NH2,        NHC₁₋₃ alkyl, NHC₁₋₃ alkanoyl, N(C₁₋₃ alkyl)₂, N(C₁₋₃        alkyl)(C₁₋₃ alkanoyl),    -   B means COOH, COOR⁵, CONH₂, CONHNH₂, CONHR⁵, CONR⁵R^(5′),        CONHOH, CONHOR⁵, SO₃H, SO₂NH₂, SO₂NHR⁵, SO₂NR⁵R^(5′), PO₃H,        PO(OH)(OR⁵), PO(OR⁵)(OR^(5′)), PO(OH)(NHR⁵), PO(NHR⁵)(NHR⁵),        tetrazolyl, in each case bonded to a carbon atom of group A, or        the entire group Y-A-B N(SO₂R⁴)(SO₂R^(4′)) or NHSO₂R⁴,    -   X means a bond, CH₂, (CH₂)₂, CH(CH₃), (CH₂)₃, CH(CH₂CH₃),        CH(CH₃)CH₂, CH₂CH(CH₃),    -   Y means O, NH, NR⁴, NCOR⁴, NSO₂R⁴, with the proviso, if Y means        NH, NR⁴, NCOR⁴ or NSO₂R⁴, and    -   a) the substituent R² contains a nitrogen-containing, saturated        heterocyclic compound, this heterocyclic compound is not        substituted in the imine nitrogen with H, methyl, ethyl, propyl        or isopropyl, or    -   b) in optionally present groups XNHR⁴ or XNR⁴R^(4′) of the        substituent R², R⁴ and/or R^(4′) does not mean C₁₋₄ alkyl,

then B does not mean COOH, SO₃H, PO₃H₂ or tetrazolyl at the same time,and R¹ and R², independently of one another, mean C₅₋₆ heteroaryl orphenyl, if the latter, independently of one another, are unsubstituted,or are substituted simply with C₁₋₆ alkyl, C₁₋₄ perfluoroalkyl, OC₁₋₆alkyl, OC₁₋₄ perfluoroalkyl, COOH, COOC₁₋₆ alkyl, COC₁₋₆ alkyl, CONH₂,CONHR⁴, NO₂, NH₂, NHCOR⁴, NHSO₂R⁴, or with 1 or 2 halogen atoms from thegroup that consists of F, Cl, Br, and I, and whereby the followingcompounds are excluded:

-   [(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]acetic acid methyl ester,-   5-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]pentanoic acid methyl    ester,-   4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]butanoic acid ethyl ester,-   5-[[1-(4-nitrophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]-pentanoic    acid methyl ester,-   6-[[1-(4-nitrophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester,-   5-[[1-(4-aminophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester,-   5-[[1-[4-[[(4-chlorophenyl)sulfonyl]amino]phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester,-   5-[[1-[4-[(acetyl)amino]phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester-   5-[[1-(3-nitrophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester,-   6-[[1-(3-nitrophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester,-   5-[[1-(3-aminophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester,-   5-[[1-[3-[[(4-chlorophenyl)sulfonyl]amino]phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester,-   5-[[1-[3-[(acetyl)amino]phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester.

The physiologically compatible salts can be formed with inorganic andorganic acids, such as, for example, oxalic acid, lactic acid, citricacid, fumaric acid, acetic acid, maleic acid, tartaric acid, phosphoricacid, HCl, HBr, sulfuric acid, p-toluenesulfonic acid, andmethanesulfonic acid.

For salt formation of acid groups, inorganic or organic bases are alsosuitable that are known for the formation of physiologically compatiblesalts, such as, for example, alkali hydroxides, sodium and potassiumhydroxide, alkaline-earth hydroxides such as calcium hydroxide, ammonia,amines such as ethanolamine, diethanolamine, triethanolamine,N-methylglucamine, tris-(hydroxymethyl)-methylamine.

An “aryl group” is defined in particular as an optionally substitutedphenyl group or biphenyl, naphthyl, indane or fluorenyl.

A heteroaryl group is built up of 5-10 skeleton atoms and can contain1-4 heteroatoms. Heteroatoms are oxygen (O), nitrogen (N) and sulfur(S). Examples of a monocyclic heteroaryl group axe pyrrolyl, thienyl,furanyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl,pyrazolyl, furazanyl, pyridyl, pyrimidinyl, pyrazinyl and pyridazinyl.Examples of a bicyclic heteroaryl group are thienoimidazolyl, indolyl,isoindolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, indazolyl,imidazopyridinyl, purinyl, quinolyl, isoquinolyl, phthalazinyl,quinazolinyl, quinaxolinyl, cinnolinyl, naphthyridinyl and pteridinyl.If the aryl groups or heteroaryl groups are part of R¹, the binding to Nof the benzimidazole is carried out via a carbon atom.

Alkyl groups can be straight-chain or branched. Examples are methyl,ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl,sec-pentyl, tert-pentyl, neopentyl, n-hexyl, sec-hexyl, heptyl, octyl,nonyl, and hexyl.

Perfluorinated alkyls are preferably CF₃ and C₂F₅.

Alkenyl groups can be straight-chain or branched. For example, thefollowing radicals can be mentioned: vinyl, 2-propenyl, 1-propenyl,2-butenyl, 1-butenyl, 1-methyl-1-propenyl, 2-methyl-2-propenyl,3-methyl-2-propenyl.

Alkinyl groups can be straight-chain or branched. Examples of this are:ethinyl, 1-propinyl, 2-propinyl, 1-butinyl, and 2-butinyl.

Cycloalkyl groups are defined respectively as cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl or cycloheptyl.

As a saturated heterocyclic compound or as a cycloalkyl with 1 or moreheteroatoms, there can be mentioned, for example: piperidine,pyrrolidine, tetrahydrofuran, morpholine, piperazine, hexahydroazepineas well as 2,6-dimethylmorpholine, N-phenylpiperazine,methoxymethylpyrrolidine, whereby the linkage with a carbon that isadjacent to the ring can be carried out with optionally present ringnitrogens.

As alkanes, alkenes and alkines for A, there can be mentioned, forexample:

straight-chain or branched alkylene with 1-8 C atoms, such as:methylene, ethylene, propylene, butylene, pentylene, etc.,1-methylethylene, 1-ethylethylene, 1-methylpropylene, 2-methylpropylene,1-methylbutylene, 2-methylbutylene, 1-ethylbutylene, 2-ethylbutylene,1-methylpentylene, 2-methylpentylene, 3-methylpentylene, etc.

Straight-chain or branched alkenylene and alkinylene with 2-8 C atomsare alkenylene groups or alkinylene groups with double and triple bondsin all possible positions as well as with all possible methyl or ethylsubstitutions. In these radicals, in each case one or two C atoms can beexchanged for O, NH, NC₁₋₃ alkyl or N—C₁₋₃ alkanoyl, whereby theexchanged group is separated from Y by at least 2 C atoms.

If two radicals are in ortho-position, they can form a common ring withthe adjacent aromatic compounds. Compounds in which N, O or S atoms arebonded to olefinic or acetylenic multiple bonds or in which several N,O, S or halogen atoms are bonded to the same aliphatic carbon atom or inwhich N-, O- or S atoms are bonded directly to one another, areexcluded, if these linkages are not explicitly defined, for example, inthe functional groups or in heteroaromatic compounds that are mentionedin the claim.

Preferred are the benzimidazoles in which:

-   -   R¹ means a monocyclic or bicyclic C₆₋₁₂ aryl group or a        monocyclic or bicyclic 5- to 10-membered heteroaryl group with        1-2 heteroatoms selected from the group that consists of N, S or        O, whereby the mentioned aryl or heteroaryl group can be        substituted with up to three of the following substituents,        independently of one another:        -   F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XCN,            XCOOH, XCOOR⁴, XCONH₂, XCONR⁴R^(4′), XCONHR⁴, XCONHOH,            XCONHOR⁴, XCOSR⁴, XSR⁴, NO₂, XNHR⁴, XNR⁴R⁴′, R⁴, whereby two            substituents at R¹, if they are in ortho-position to one            another, can be linked to one another in such a way that            they jointly form methanediylbisoxy, ethane-1,2-diylbisoxy,            propane-1,3-diyl, butane-1,4-diyl.

Preferred are also benzimidazoles, in which

-   -   R² means a monocyclic or bicyclic C₆₋₁₀ aryl group or a        monocyclic or bicyclic 5- to 10-membered heteroaryl group with        1-2 heteroatoms selected from the group that consists of N, S or        O, whereby the mentioned aryl or heteroaryl group can be        substituted with up to three of the following substituents,        independently of one another:        -   F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴,            XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCOOH,            XCOOR⁴, XCONH₂, XCONHR⁴, XCONR⁴R^(4′), XCONHOH, XCONHOR⁴,            XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′),            NO₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XN(SO₂R⁴)SO₂R^(4′),            XNR⁴SO₂R^(4′), R⁴, whereby two substituents at R², if they            are in ortho-position to one another, can be linked to one            another in such a way that they jointly form            methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl,            butane-1,4-diyl.

Also preferred are benzimidazoles of general formula I, in which

-   -   R³ means one or two substituents, which, independently of one        another, can be:        -   hydrogen, F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴,            XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCN,            XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂,            XNH₂, XNHR⁴, XNR⁴N^(4′), XNHSO₂R⁴, XNR⁴SO₂R^(4′),            XN(SO₂R⁴)SO₂R^(4′), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, or R⁴,            whereby two substituents R³, if they are in ortho-position            to one another, can be linked to one another in such a way            that they jointly form methanediylbisoxy,            ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl.

Preferred are also benzimidazoles of general formula I, in which

-   -   R⁴ and R^(4′), independently of one another, mean CF₃, C₂F₅,        C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkinyl, C₃₋₆ cycloalkyl, (C₁₋₃        alkyl-C₃₋₆ cycloalkyl), phenyl or 5- to 6-membered heteroaryl        with 1-2 N, S or O atoms, whereby the phenyl and heteroaryl        groups can be substituted with one or two substituents from the        group that consists of F, Cl, Br, CH₃, C₂H₅, OCH₃, OC₂H₅, CF₃,        C₂F₅,    -   and in addition in a 5-membered cycloalkyl ring, a ring member        can be an N or an O, and in a 6-membered cycloalkyl ring, one or        two ring members can be N and/or O, whereby ring nitrogens        optionally can be substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl.

Also preferred are benzimidazoles of general formula I, in which

-   -   R⁵ and R^(5′), independently of one another, can be C₁₋₆ alkyl,        whereby a carbon atom can be exchanged for O, NH, NC₁₋₃ alkyl,        NC₁₋₃ alkanoyl, C₃₋₇ cycloalkyl-C₀₋₃ alkyl, whereby in a        5-membered cycloalkyl ring, a ring member can be an N or an O,        and in a 6- or 7-membered cycloalkyl ring, one or two ring        members can be N and/or O, whereby ring nitrogens optionally can        be substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, whereby the        mentioned C₁₋₆ alkyl part can be substituted with one of the        previously mentioned cycloalkyls or else a 5- to 6-membered        heteroaromatic compound with 1-2 heteroatoms, selected from N, S        or O,        -   whereby all previously mentioned alkyl and cycloalkyl parts            can be substituted with up to two substituents that consist            of CF₃, OH, OC₁₋₃ alkyl, and the previously mentioned            heteroaryl groups with one or two substituents that consist            of F, Cl, CF₃, CH₃, C₂H₅, OCH₃, OC₂H₅ or R⁵ and R^(5′)            together with the nitrogen atom form a 5- to 7-membered            heterocyclic compound, which can contain another oxygen,            nitrogen or sulfur atom and can be substituted with C₁₋₄            alkyl, C₁₋₄ alkoxy-C₀₋₂ alkyl, C₁₋₄ alkoxy-carbonyl,            aminocarbonyl or phenyl.

Preferred are also benzimidazoles of general formulae I, in which

-   -   A means C₁₋₁₀ alkanediyl, C₂₋₁₀ alkenediyl, C₂₋₁₀ alkinediyl,        (C₀₋₅ alkanediyl-C₃₋₇ cycloalkanediyl-C₀₋₅ alkanediyl), whereby        in a 5-membered cycloalkyl ring, a ring member can be an N or an        O, or in a 6- or 7-membered cycloalkyl ring, one or two ring        members can be N and/or O, whereby ring nitrogens optionally can        be substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, whereby in the        above-mentioned aliphatic chains, a carbon atom or two carbon        atoms can be exchanged for O, NH, NC₁₋₃ alkyl, or NC₁₋₃        alkanoyl.

Also preferred are benzimidazoles of general formula I, in which

-   -   B means COOH, COOR⁵, CONH₂, CONHR⁵, CONR⁵R^(5′), CONHOH, CONHOR⁵        or tetrazolyl, in each case bonded to a carbon atom of group A.    -   B in the meaning of COOR⁵, CONH₂, CONHR⁵, CONR⁵ or R^(5′) is        especially preferred.

Preferred are also benzimidazoles of general formula I, in which

-   -   X means a bond or methylene.

Preferred are also benzimidazoles of general formula I, in which

-   -   Y means O.        -   In particular, R¹ and R², independently of one another, mean            phenyl or 5- to 6-membered heteroaryl, with 1-2 heteroatoms            such as N, O or S atoms, which can be substituted with F,            Cl, Br, cyano, C₁₋₄ alkyl, C₁₋₄ alkoxy, methylenedioxy, C₁₋₄            alkylthio, NO₂, CF₃, NH₂, NH (C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂.        -   The meaning of H, F, Cl, OH, C₁₋₄ alkoxy, C₁₋₄ alkyl, NO₂,            NH₂, NH—C₁₋₄ alkanoyl NH—SO₂-benzyl or NH—SO₂-phenyl,            whereby the phenyl radical can be substituted with F, Cl,            BR, C₁₋₄ alkyl, C₁₋₄ alkoxy, CF₃ or acetylamino, is            especially preferred for R³.

Especially preferred are the following benzimidazoles:

-   [(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]acetic acid isopropyl ester-   3-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]propanoic acid methyl    ester-   2-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]propanoic acid methyl    ester-   4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]butanoic acid isopropyl    ester-   5-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]pentanoic acid isopropyl    ester-   6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acid methyl ester-   6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acid isopropyl    ester-   6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-methoxy-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-(phenylmethoxy)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-hydroxy-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   7-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]heptanoic acid methyl    ester-   6-[[1-(3-nitrophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[2-phenyl-1-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-phenyl-1-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-(3-cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(3-cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-(3-cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid-   6-[[1-(4-cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-(3-chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(3-chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-(4-chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-(3-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(3-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(3,5-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(3,5-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-(3-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(3,4-dimethoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-[3,4-(methylenedioxy)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-[3,4-(methylenedioxy)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid-   6-[[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid-   6-[[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-[4-(N,N-dimethylamino)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-[4-(N,N-dimethylamino)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid-   6-[[1-phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[2-(3-chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-(3-chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[2-(4-chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-(4-chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[2-(4-methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-(4-methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1-phenyl-2-(4-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid    methyl ester-   6-[(1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl)oxy]hexanoic acid    methyl ester-   6-[(1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl)oxy]hexanoic acid    isopropyl ester-   6-[[5-[[(4-bromophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1,2-diphenyl-5-[[(3-methylphenyl)sulfonyl]amino]-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1,2-diphenyl-5-[[(4-methylphenyl)sulfonyl]amino]-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1,2-diphenyl-5-[[(4-methoxyphenyl)sulfonyl]amino]-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1,2-diphenyl-5-[[[(4-trifluoromethyl)phenyl]sulfonyl]amino]-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[5-[[[4-(acetylamino)phenyl]sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]-hexanoic    acid isopropyl ester-   6-[[5-[[bis(3-chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[1,2-diphenyl-5-[(propylsulfonyl)amino]-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[5-[(benzylsulfonyl)amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   2-[2-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]acetic acid    methyl ester-   3-[2-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]propanoic acid    methyl ester-   6-[[1-(3-nitrophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid ethyl ester-   6-[[4-acetyl-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoic    acid methyl ester-   6-[[2-phenyl-1-[4-(thiomethyl)phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic    acid methyl ester-   6-[[2-phenyl-1-[(4-(thiomethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-phenyl-1-(3-thienyl)-1H-benzimidazol-5-yl]oxy]hexanoic acid    methyl ester-   6-[[2-phenyl-1-(3-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid    methyl ester-   4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]butanoic acid methyl ester-   N-(phenylmethoxy)-6-[[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]-hexanamide-   N,N-dimethyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-isopropyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]-1-pyrrolidin-1-ylhexan-1-one-   5-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester-   6-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[4-(acetyloxy)-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[4-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[4-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid-   -6-[[7-methyl-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-phenyl-1-(3-pyridyl)-1H-benzimidazol-5-yl]oxy]hexanoic acid    methyl ester-   6-[[2-phenyl-1-(3-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid    methyl ester-   6-[[2-phenyl-1-(4-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid    methyl ester-   6-[[2-(4-fluoro-phenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-(4-methoxyphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]-hexanoic    acid methyl ester-   6-[[2-(4-bromophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-[4-(trifluoromethyl)phenyl]-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-phenyl-2-(benzothien-2-yl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-phenyl-2-(benzothien-2-yl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid-   6-[[5-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[5-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid-   6-[[5-methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid isopropyl ester-   6-[[5-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[5-methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester benzimidazol-6-yl]oxy]hexanoic acid methyl ester-   6-[[5-[[(4-chlorophenyl)sulfonyl]amino]-2-(4-fluorophenyl)-1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-(4-methoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   4-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]butanoic    acid methyl ester-   5-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester-   5-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]pentanoic    acid methyl ester-   6-[[5-[[(4-(trifluoromethyl)phenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[5-[[(4-chlorophenyl)sulfonyl]methylamino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(indan-5-yl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid    methyl ester-   6-[[1-(indan-5-yl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid-   6-[[1-(3-fluorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-(4-nitrophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-phenyl-2-(3-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid    methyl ester-   N-(cyclopropylmethoxy)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-isobutoxy-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-(cyclopropylmethoxy)-6-[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl)oxy]-hexanamide-   N-isobutoxy-6-[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl)oxy]hexanamide-   N-(2-methoxyethyl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-(3-methoxypropyl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-isobutyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]-1-morpholin-1-ylhexan-1-one-   N,N-di(-2-methoxyethyl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-isopentyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-(pyridin-2-yl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-(pyridin-3-yl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide-   N-isopropyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide-   N,N-dimethyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide-   N,N-diethyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide-   N-isobutyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide-   N-cyclopropyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide-   N-cyclobutyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide-   N-tert-butyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide-   (R)-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]1-(2-methoxymethyl)-pyrrolidin-1-ylhexan-1-one-   N-(3-imidazol-1-yl-propyl)-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide-   N-(2-pyridin-2-ylethyl)-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide-   N-(3-methoxypropyl)-6-[[1-(indan-5-yl)-2-phenyl-1H-benzimidazol-6-yl]oxy]heptanamide-   6-[[1-(4-methylphenyl)-2-(3-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-methylphenyl)-2-(4-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-methylphenyl)-2-(2-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-methylphenyl)-2-(3-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[2-(3-indolyl)-1-(4-methylphenyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-methylphenyl)-2-(2-furyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-methylphenyl)-2-(3-furyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester-   6-[[1-(4-methylphenyl)-2-(5-methyl-2-thienyl) 1H    benzimidazol-6-yl]oxy]hexanoic acid methyl ester-   6-[[1-(4-methylphenyl)-2-(3-methyl-2-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoic    acid methyl ester.

The benzimidazole derivatives according to the invention inhibit theactivation of microglia and can therefore be used for the production ofa pharmaceutical agent for treatment or prevention of diseases that areassociated with microglia. Microglia are defined here as the macrophagesof the brain.

This action is surprising since to date benzimidazole derivatives hadbeen described only for the treatment of thromboses and arteriosclerosis(EP0531883, WO98/07263, EP0104727, WO97/12613), cystitis (WO97/33873)and diseases that are linked to a β-amyloid peptide (U.S. Pat. No.5,552,426) and increased activation of Ca-channels (EP520200), but aneffect on microglia is not known.

The invention also relates to the use of a benzimidazole of generalformula II

in which

-   -   R¹ means a monocyclic or bicyclic C₆₋₁₂ aryl group or a        monocyclic or bicyclic 5- to 10-membered heteroaryl group with        1-4 heteroatoms selected from the group that consists of N, S or        O, whereby the mentioned aryl or heteroaryl group can be        substituted with up to three of the following substituents,        independently of one another:        -   F, Cl, Br, I, C(NH)NH₂, C(NH)NHR⁴, C(NH)NR⁴R^(4′),            C(NR⁴)NH₂, C(NR⁴)NHR^(4′), C(NR⁴)NR⁴R^(4′), XOH, XOR⁴,            XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XOCR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′),            XC(NO(COR⁴))R^(4′), XCN, XCOOH, XCOOR⁴, XCONH₂,            XCONR⁴R^(4′), XCONHR⁴, XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴,            XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂,            XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XN(SO₂R⁴)(SO₂R^(4′)),            XNR⁴SO₂R^(4′), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴,            tetrahydro-2,5-dioxopyrrol-1-yl,            2,5-dihydro-2,5-dioxopyrrol-1-yl,            2,7-dihydro-2,7-dioxoisoindol-1-yl, R⁴, whereby two            substituents at R¹, if they are in ortho-position to one            another, can be linked to one another in such a way that            they jointly form methanediylbisoxy, ethane-1,2-diylbisoxy,            propane-1,3-diyl, butane-1,4-diyl,    -   R² means a monocyclic or bicyclic C₆₋₁₀ aryl group or a        monocyclic or bicyclic 5- to 10-membered heteroaryl group with        1-4 heteroatoms selected from the group that consists of N, S or        O, whereby the mentioned aryl or heteroaryl group can be        substituted with up to three of the following substituents,        independently of one another:        -   F, Cl, Br, I, C(NH)NH₂, C(NH)NHR⁴, C(NH)NR⁴R^(4′),            C(NR⁴)NH₂, C(NR⁴)NHR^(4′), C(NR⁴)NR⁴R^(4′), XOH, XOR⁴,            XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′),            XC(NO(COR⁴))R^(4′), XCN, XCOOH, XCOOR⁴, XCONH₂,            XCONR⁴R^(4′), XCONHR⁴, XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴,            XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂,            XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XN(SO₂R⁴)(SO₂R^(4′)),            XNR⁴SO₂R^(4′), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴,            tetrahydro-2,5-dioxopyrrol-1-yl,            2,5-dihydro-2,5-dioxopyrrol-1-yl,            2,7-dihydro-2,7-dioxoisoindol-1-yl, R⁴, whereby two            substituents at R², if they are in ortho-position to one            another, can be linked to one another in such a way that            they jointly form methanediylbisoxy, ethane-1,2-diylbisoxy,            propane-1,3-diyl, butane-1,4-diyl,    -   R³ stands for one or two substituents, that mean, independently        of one another:        -   hydrogen, F, Cl, Br, I, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴,            XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′),            XC(NO(COR⁴))R^(4′), XCN, XCOOH, XCOOR⁴, XCONH₂, XCONHR⁴,            XCONR⁴R^(4′), XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴,            XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴,            XNR⁴R^(4′), XNHSO₂R⁴, XNR⁴SO₂R^(4′), XN(SO₂R⁴)(SO₂R^(4′)),            XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴,            tetrahydro-2,5-dioxopyrrol-1-yl,            2,5-dihydro-2,5-dioxopyrrol-1-yl,            2,7-dihydro-2,7-dioxoisoindol-1-yl, R⁴, whereby two            substituents R³, if they are in ortho-position to one            another, can be linked to one another in such a way that            they jointly form methanediylbisoxy, ethane-1,2-diylbisoxy,            propane-1,3-diyl, butane-1,4-diyl,    -   R⁴ and R^(4′), independently of one another, mean C₁₋₄        perfluoroalky, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkinyl, C₃₋₇        cycloalkyl, (C₁₋₃ alkyl-C₃₋₇ cycloalkyl), C₁₋₃ alkyl-C₆₋₁₀ aryl,        C₁₋₃ alkyl 5- to 10-membered heteroaryl with 1-4 N, S or O atoms        heteroaryl, C₆₋₁₀ aryl or 5- to 10-membered heteroaryl with 1-4        N, S or O atoms, whereby the C₆₋₁₀ aryl and heteroaryl groups        can be substituted with one or two substituents from the group        that consists of F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅, CF₃,        C₂F₅ or else can carry an annelated methanediylbisoxy group or        ethane-1,2-diylbisoxy group, whereby in a 5-membered cycloalkyl        ring, a ring member can be an N or an O, and in a 6- or        7-membered cycloalkyl ring, one or two ring members can be N or        O, whereby ring nitrogens optionally can be substituted with        C₁₋₃ alkyl or C₁₋₃ alkanoyl,    -   R⁵ and R^(5′), independently of one another, mean hydrogen, C₁₋₆        alkyl, C₂₋₆ alkenyl, C₂₋₆ alkinyl, whereby a carbon atom can be        exchanged for O, S, SO, SO₂, NH, NC₁₋₃ alkyl or NC₁₋₃ alkanoyl,        C₃₋₇ cycloalkyl-C₀₋₃ alkyl, whereby in a 5-membered cycloalkyl        ring, a ring member can be an N or an O and in a 6- or        7-membered cycloalkyl ring, one or two ring members can be N        and/or O, whereby ring nitrogens optionally can be substituted        with C₁₋₃ alkyl or C₁₋₃ alkanoyl, C₆₋₁₀ aryl or 5- to        10-membered heteroaryl with 1-4 heteroatoms from N, S, and O,        whereby the mentioned alkyl, alkenyl, and alkinyl chains can be        substituted with one of the previously mentioned cycloalkyls,        aryls or heteroaryls, whereby all previously mentioned alkyl and        cycloalkyl radicals with up to two substituents consisting of        CF₃, C₂F₅, OH, OC₁₋₃ alkyl, NH2, NHC₁₋₃ alkyl, NHC₁₋₃ alkanoyl,        N(C₁₋₃ alkyl)₂N(C₁₋₃ alkyl) (C₁₋₃ alkanoyl), COOH, CONH₂,        COOC₁₋₃ alkyl and all previously mentioned aryl and heteroaryl        groups can be substituted with one or two substituents from the        group that consists of F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅,        CF₃, C₂F₅ or else can carry an annelated methanediylbisoxy,        ethane-1,2-diylbisoxy group, or R⁵ and R^(5′) together with the        nitrogen atom form a 5- to 7-membered heterocyclic compound,        which can contain another oxygen, nitrogen or sulfur atom and        can be substituted with C₁₋₄ alkyl, C₁₋₄ alkoxy-C₀₋₂ alkyl, C₁₋₄        alkoxy-carbonyl, aminocarbonyl or phenyl,    -   A means C₁₋₁₀ alkanediyl, C₂₋₁₀ alkenediyl, C₂₋₁₀ alkinediyl,        (C₀₋₅ alkanediyl-C₃₋₇ cycloalkanediyl-C₀₋₅ alkanediyl), (C₀₋₅        alkanediylarylene-C₀₋₅ alkanediyl), (C₀₋₅        alkanediyl-heteroarylene-C₀₋₅ alkanediyl), whereby the aryl and        heteroaryl groups can be substituted with one or two        substituents that consist of F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃,        OC₂H₅, CF₃, C₂F₅, whereby in a 5-membered cycloalkyl ring, a        ring member can be an N or an O, and in a 6- or 7-membered        cycloalkyl ring, one or two ring members can be N and/or O,        whereby ring nitrogens optionally can be substituted with C₁₋₃        alkyl or C₁₋₃ alkanoyl, whereby in the mentioned aliphatic        chains, a carbon atom or two carbon atoms can be exchanged for        O, NH, NR⁴, NCOR⁴, NSO₂R⁴, and whereby alkyl or cycloalkyl        groups can be substituted with up to two substituents consisting        of F, OH, OR⁴, OCOR⁴, ═O, NH₂, NR⁴R^(4′), NHCOR⁴, NHCOOR⁴,        NHCONHR⁴, NHSO₂R⁴SH, SR⁴,    -   B means hydrogen, OH, OCOR⁵, OCONHR⁵, OCOOR⁵, COR⁵, C(NOH)R⁵,        C(NOR⁵)R^(5′), C(NO(COR⁵))R^(5′), COOH, COOR⁵, CONH₂, CONHNH₂,        CONHR⁵, CONR⁵R^(5′), CONHOH, CONHOR⁵, SO₃H, SO₂NH₂, SO₂NHR⁵,        SO₂NR⁵R^(5′), PO₃H, PO(OH)(OR⁵), PO(OR⁵)(OR^(5′)), PO(OH)(NHR⁵),        PO(NHR⁵)(NHR^(5′)), tetrazolyl, respectively bonded to a carbon        atom of group A, or the entire group Y-A-B N(SO₂R⁴)(SO₂R^(4′))        or NHSO₂R⁴,    -   X means a bond, CH₂, (CH₂)₂, CH(CH₃), (CH₂)₃, CH(CH₂CH₃),        CH(CH₃)CH₂, CH₂CH(CH₃),    -   Y means a bond, O, S, SO, SO₂, NH, NR⁴, NCOR⁴, NSO₂R⁴, for the        production of a pharmaceutical agent for treating or preventing        diseases that are associated with a microglia activation.

In addition to the new compounds of general formula I, general formulaII also comprises known compounds (EP 0 531 883, DE 4330959). Thecompounds of general formula II according to the invention inhibit theactivation of the microglia activation. This action is also new for theknown compounds.

Preferred is the use of compounds of general formula II, whereby

-   -   R¹ means a monocyclic or bicyclic aryl group or a monocyclic or        bicyclic 5- to 10-membered heteroaryl group with 1-2 heteroatoms        selected from the group that consists of N, S or O, whereby the        mentioned aryl or heteroaryl group can be substituted with up to        three of the following substituents, independently of one        another:        -   F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XCN,            XCOOH, XCOOR⁴, XCONH₂, XCONR⁴R^(4′), XCONHR⁴, XCONHOH,            XCONHOR⁴, XCOSR⁴, XSR⁴, NO₂, XNHR⁴, XNR⁴R^(4′), R⁴, whereby            two substituents at R¹, if they are in ortho-position to one            another, can be linked to one another in such a way that            they jointly form methanediylbisoxy, ethane-1,2-diylbisoxy,            propane-1,3-diyl, butane-1,4-diyl.

Also preferred is the use of compounds of general formula II, whereby

-   -   R² means a monocyclic or bicyclic aryl group or a monocyclic or        bicyclic 5- to 10-membered heteroaryl group with 1-2 heteroatoms        selected from the group that consists of N, S or O, whereby the        mentioned aryl group or heteroaryl group can be substituted with        up to three of the following substituents, independently of one        another:        -   F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴,            XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCN, XCOOH,            XCOOR⁴, XCONH₂, XCONR⁴R^(4′), XCONHR⁴, XCONHOH, XCONHOR⁴,            XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′),            NO₂, XNH₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XN(SO₂R⁴)            (SO₂R^(4′)), XNR⁴SO₂R^(4′), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴,            R⁴, whereby two substituents at R², if they are in            ortho-position to one another, can be linked to one another            in such a way that they jointly form methanediylbisoxy,            ethane-1,2-diylbisoxy, propane-1,3-diyl, butane-1,4-diyl.

Also preferred is the use of compounds of general formula II, whereby

-   -   R³ stands for one or two substituents, which independently of        one another, mean:        -   hydrogen, F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴,            XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCN,            XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂,            XNH₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XNR⁴SO₂R^(4′),            XN(SO₂R⁴)(SO₂R^(4′)), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, or R⁴,            whereby two substituents R³, if they are in ortho-position            to one another, can be linked to one another in such a way            that they jointly form methanediylbisoxy,            ethane-1,2-diylbisoxy, propane-1,3-diyl, butane-1,4-diyl.

Also preferred is the use of compounds of general formula II whereby

-   -   R⁴ and R^(4′), independently of one another, mean CF₃, C₂F₅,        C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkinyl, C₃₋₆ cycloalkyl, (C₁₋₃        alkyl-C₃₋₆ cycloalkyl), C₁₋₃ alkylaryl, C₁₋₃ alkylheteroaryl,        monocyclic aryl or 5- to 6-membered heteroaryl with 1-2 N, S or        O atoms, whereby the aryl and heteroaryl groups can be        substituted with one or two substituents from the group that        consists of F, Cl, Br, CH₃, C₂H₅, OCH₃, OC₂H₅, CF₃, C₂F₅ or else        can carry an annelated methanediylbisoxy or        ethane-1,2-diylbisoxy group, and in addition in a 5-membered        cycloalkyl ring, a ring member can be an N or an O, and in a        6-membered cycloalkyl ring, one or two ring members can be N        and/or O, whereby ring nitrogens optionally can be substituted        with C₁₋₃ alkyl or C₁₋₃ alkanoyl.

Also preferred is the use of compounds of general formula II, in which

-   -   R⁵ and R^(5′), independently of one another, can be C₁₋₆ alkyl,        whereby a carbon atom can be exchanged for O, NH, NC₁₋₃ alkyl,        NC₁₋₃ alkanoyl, C₃₋₇ cycloalkyl-C₀₋₃ alkyl, whereby in a        5-membered cycloalkyl ring, a ring member can be an N or an O,        and in a 6- or 7-membered cycloalkyl ring, one or two ring        members can be N and/or O, whereby ring nitrogens optionally can        be substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, whereby the        mentioned C₁₋₆ alkyl part can be substituted with one of the        previously mentioned cycloalkyls or else a 5- to 6-membered        heteroaromatic compound with 1-2 heteroatoms, selected from the        group that consists of N, S or O, whereby all previously        mentioned alkyl and cycloalkyl parts can be substituted with up        to two substituents that consist of CF₃, OH, OC₁₋₃ alkyl, and        the previously mentioned heteroaryl groups can be substituted        with one or two substituents that consist of F, Cl, CF₃, CH₃,        C₂H₅, OCH₃, OC₂H₅, or R⁵ and R^(5′) together with the nitrogen        atom form a 5- to 7-membered heterocyclic compound, which can        contain another oxygen, nitrogen or sulfur atom and can be        substituted with C₁₋₄ alkyl, C₁₋₄ alkoxy-C₀₋₂ alkyl, C₁₋₄        alkoxy-carbonyl, aminocarbonyl or phenyl.

Also preferred is the use of compounds of general formula II, whereby

-   -   A means C₁₋₁₀ alkanediyl, C₂₋₁₀ alkenediyl, C₂₋₁₀ alkinediyl,        (C₀₋₅ alkanediyl-C₃₋₇ cycloalkanediyl-C₀₋₅ alkanediyl), or (C₀₋₅        alkanediyl-heteroarylene-C₀₋₅ alkanediyl), whereby an optionally        present heteroaryl group can be substituted with one or two        substituents that consist of F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃,        OC₂H₅, CF₃, C₂F₅, and in addition in a 5-membered cycloalkyl        ring, a ring member can be an N or an O, and in a 6- or        7-membered cycloalkyl ring, one or two ring members can be N        and/or O, whereby ring nitrogens optionally can be substituted        with C₁₋₃ alkyl or C₁₋₃ alkanoyl, whereby in an aliphatic chain,        a carbon atom or two carbon atoms can be exchanged for O, NH,        NC₁₋₃ alkyl, NC₁₋₃ alkanoyl, NSO₂C₁₋₃ alkyl, and whereby alkyl        or cycloalkyl parts can be substituted with up to two F atoms or        one of the substituents that consists of OH, OC₁₋₃ alkyl, OC₁₋₃        alkanoyl, ═O, NH₂, NHC₁₋₃ alkyl, N(C₁₋₃ alkyl), NHC₁₋₃ alkanoyl,        N(C₁₋₃ alkyl)(C₁₋₃ alkanoyl), NHCOOC₁₋₃ alkyl, NHCONHC₁₋₃ alkyl,        NHSO₂C₁₋₃ alkyl, SH, SC₁₋₃ alkyl.

Also preferred is the use of the compounds of general formula II,whereby

-   -   B means hydrogen, OH, OCOR⁵, OCONHR⁵, OCOOR⁵, COOH, COOR⁵,        CONH₂, CONHR⁵, CONR⁵R^(5′), CONHOH, CONHOR⁵, or tetrazolyl, in        each case bonded to a carbon atom of group A.

Also preferred is the use of compounds of general formula II, whereby

-   -   X means a bond or CH₂.

Also preferred is the use of compounds of general formula II, whereby

-   -   Y means a bond, O, S, NH, NR⁴, NCOR⁴ or NSO₂R⁴.

Example 307 describes how the inhibition of the microglia activation canbe measured. In this case, the activation of the microglia can becarried out by various stimuli, such as, e.g., Aβ-peptide (β-amyloid,Araujo, D. M. and Cotman, C. M. Brain Res. 569, 141-145 (1992)), prionprotein, cytokines or by cell fragments (Combs, C. K. et al. (1999) J.Neurosci., 19, 928-939, Wood, P. L. (1998) Neuroinflammation: Mechanismsand Management, Humana Press). For example, the compound of Example 49,6-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester indicates an inhibition of IC₅₀=0.75 μm.

The stimulation with the Aβ-peptide corresponds to thepathophysiological situation in Alzheimer's disease. In this test, thesubstances according to the invention showed inhibition of microgliaactivation in the case of stimulation with the Aβ-peptide. Theinhibition of the microglia activation by the substances according tothe invention results in a strong reduction of the cytokine productionand secretion, e.g., of II1β and TNFα (measured by ELISA and mRNAexpression analysis) and in a reduced secretion of reactiveoxygen/nitrogen intermediate products. Several inflammation factors arethus equally inhibited.

The in vivo action of the substances according to the invention wasshown in an MCAO model in rats. This model simulates the state of astroke. The substances according to the invention reduce the microgliaactivation, which occurs in the case of active brain lesions in thebrains of animals.

The invention also relates to the use of the compounds of generalformula I and of general formula II according to the invention for theproduction of a pharmaceutical agent for treating or preventing diseasesthat are associated with a microglia activation. Examples of suchdiseases are AIDS dementia, amyotrophic lateral sclerosis,Creutzfeldt-Jacob disease, Down's syndrome, diffuse Lewy body's disease,Huntington's disease, leukoencephalopathy, multiple sclerosis,Parkinson's disease, Pick's disease, Alzheimer's disease, stroke,temporary lobe epilepsy and tumors.

The invention also relates to pharmaceutical agents that contain one ormore compounds of general formula I according to the invention and oneor more vehicles. The pharmaceutical agents or compositions of theinvention are produced in a way that is known per se with the commonlyused solid or liquid vehicles or diluents and the commonly usedpharmaceutical and technical adjuvants corresponding to the desired typeof administration with a suitable dosage. The preferred preparationsconsist of a form for dispensing that is suitable for oral, enteral orparenteral administration. Such forms for dispensing are, for example,tablets, film tablets, coated tablets, pills, capsules, powders or depotforms as well as suppositories. Corresponding tablets can be obtained,for example, by mixing active ingredient with known adjuvants, forexample inert diluents such as dextrose, sugar, sorbitol, mannitol,polyvinylpyrrolidone, explosives such as corn starch or alginic acid,binders such as starch or gelatin, lubricants such ascarboxypolymethylene, carboxy methyl cellulose, cellulose acetatephthalate or polyvinyl acetate. The tablets can also consist of severallayers.

Coated tablets can be produced accordingly by coating cores that areproduced analogously to the tablets with agents that are commonly usedin coated tablet coatings, for example polyvinylpyrrolidone or shellac,gum arabic, talc, titanium oxide or sugar. In this case, the shell ofthe coated tablet can also consist of several layers, whereby theadjuvants that are mentioned above in the case of the tablets can beused. Capsules that contain active ingredients can also be produced, forexample, by the active ingredient being mixed with an inert vehicle suchas lactose or sorbitol and encapsulated in gelatin capsules.

The substances according to the invention can also be used in suitablesolutions such as, for example, physiological common salt solution, asinfusion or injection solutions.

For parenteral administration, in particular oily solutions, such as,for example, solutions in sesame oil, castor oil and cottonseed oil, aresuitable. To increase solubility, solubilizers can be added, such as,for example, benzyl benzoate or benzyl alcohol.

It is also possible to incorporate the substances according to theinvention in a transdermal system and to administer them transdermally.

The dosage of the substances of general formula I and of general formulaII according to the invention is determined by the attending physicianand depends on, i.a., the substance that is administered, the method ofadministration, the disease that is to be treated and the severity ofthe disease. The daily dose is no more than 1000 mg, preferably no morethan 100 mg, whereby the dose can be given as a single dose to beadministered once or divided into 2 or more daily doses.

The compounds of formula I can be present as tautomers, stereoisomers orgeometric isomers. The invention also comprises all possible isomers,such as E- and Z-isomers, S- and R-enantiomers, diastereomers, racematesand mixtures thereof including the tautomeric compounds.

The isomer mixtures can be separated into enantiomers or E/Z isomersaccording to commonly used methods, such as, for example,crystallization, chromatography or salt formation.

The production of the compounds according to the invention is carriedout analogously to known processes that are described in, for example,EP 531 883. If the production of the starting compounds is notdescribed, the starting compounds are known and are commerciallyavailable or their production is carried out analogously to theprocesses described here. Below, the production of some precursors,intermediate products and products is described by way of example.

In the production of the substances according to the invention, forexample, the following processes are used:

General Operating Instructions 1:

Reduction Nitro Groups, Hydrogenation of Olefinic Double Bonds andHydrogenolytic Cleavage of Benzyl Ethers

The compound that is to be reduced is dissolved in ethyl acetate,tetrahydrofuran, methanol or ethanol or mixtures of the solvent, and itis hydrogenated to 2-5% (relative to the nitro compound) palladium oncarbon (10%) at normal pressure. After hydrogen absorption has ended, itis suctioned off, the residue is washed with ethyl acetate or methanolor ethanol, and the filtrate is concentrated by evaporation in a vacuum.The crude product is reacted generally without further purification.

General Operating Instructions 2:

Reduction Nitro Groups

9.2 g of iron(II) sulfate is introduced into 30 ml of water and 9 ml ofammonia solution. A solution of 3.6 mmol of the nitro compound in 100 mlof ethanol is added in drops to it, and the suspension is stirredintensively for 1 hour at 70° C. Then, it is allowed to settle, solid isfiltered out, the filtrate is concentrated by evaporation to a largeextent, mixed with water and extracted three times with ethyl acetate.The combined extracts are dried on sodium sulfate and concentrated byevaporation in a vacuum. The amino compound is further processed as acrude product.

General Operating Instructions 3:

Cyclization to Benzimidazoles with Orthoesters

10 mmol of a 1,2-diaminobenzene derivative is dissolved in 25 ml ofethanol. 47 ml of an 0.8 M ethereal HCl solution is added in drops toit, it is stirred for 30 minutes and then evaporated to the dry state ina vacuum. The residue is taken up in 230 ml of methanol and mixed with 6ml of trimethyl orthobenzoate or the corresponding amount of anotherorthoester. It is refluxed for 2-8 hours, poured onto saturated sodiumbicarbonate solution after cooling, extracted three times with ethylacetate, the combined extracts are dried on sodium sulfate andconcentrated by evaporation in a vacuum. The residue is purified bycrystallization or column chromatography on silica gel.

General Operating Instructions 4:

Cyclization to Benzimidazoles with Imino Ester Hydrochlorides

1.2 mmol of a 1,2-diaminobenzene derivative is dissolved in 5 ml oftetrahydrofuran, mixed with 1.5 mmol of a benzimidate hydrochloride, andthe mixture is stirred for 15 hours. The batch is mixed with saturatedsodium bicarbonate solution, diluted with water and extracted threetimes with ethyl acetate. The combined organic phases are washed threetimes with 1N aqueous hydrochloric acid and once with saturated sodiumchloride solution, dried on sodium sulfate, filtered on one frit withsilica gel, and the solution is evaporated to the dry state. The productcrystallizes from diisopropyl ether.

General Operating Instructions 5:

Cyclization to Benzimidazoles Via Carboxylic Acid Anilides

4.7 mmol of a 1,2-diaminobenzene derivative is dissolved in 20 ml ofdichloromethane, mixed with 14 mmol of triethylamine and mixed slowlywith 6 mmol of carboxylic acid chloride, and the mixture is stirred for15 hours. The batch is mixed with saturated sodium bicarbonate solution,diluted with water and extracted twice with dichloromethane. Thecombined organic phases are washed with water and with saturated sodiumchloride solution, dried on sodium sulfate and concentrated byevaporation in a vacuum. The remaining crude carboxylic acid anilide istaken up in a 9:1 mixture that consists of methanol and concentratedhydrochloric acid and refluxed for 1 hour. The reaction mixture isslowly introduced into saturated sodium bicarbonate solution aftercooling, diluted with water and extracted three times withdichloromethane. The combined organic phases are washed with saturatedsodium chloride solution, dried on sodium sulfate and concentrated byevaporation in a vacuum. The residue is purified, if necessary, bycrystallization or column chromatography on silica gel.

General Operating Instructions 6:

Ether Cleavage with Hydrobromic Acid

5 g of arylmethylether is mixed with 160 ml of 48% aqueous HBr andrefluxed for 1-5 hours. After cooling, it is filtered. The residue istaken up in ethyl acetate, and it is extracted three times withsaturated sodium bicarbonate solution. After drying on sodium sulfate,it is concentrated by evaporation in a vacuum. The residue is purified,if necessary, by crystallization or column chromatography on-silica gel.

General Operating Instructions 7:

Ether Cleavage with Boron Tribromide

1.86 mmol of aryl methyl ether is dissolved in 18 ml of dichloromethaneand mixed slowly at −35° C. with 7.4 ml of a 1 M solution of borontribromide in dichloromethane. It is left for 12-15 hours at −30° C.,then mixed with saturated sodium bicarbonate solution, extracted threetimes with dichloromethane, the combined extracts are dried on sodiumsulfate and concentrated by evaporation in a vacuum. The residue ispurified, if necessary, by column chromatography on silica gel.

General Operating Instructions 8:

Akylation of Hydroxybenzimidazole Derivatives and Phenol Derivativeswith Alkyl Halides

A solution of 1.85 mmol of the hydroxybenzimidazole derivative in 12 mlof N,N-dimethylformamide is mixed with 1.85 mmol of cesium carbonate,and 2.24 mmol of alkyl bromide or alkyl iodide. When alkyl bromides areused, optionally 1.85 mmol of sodium iodide is added. It is stirred for12-96 hours, then poured onto water, taken up with ethyl acetate, theorganic phase is washed four times with water, dried on sodium sulfateand concentrated by evaporation in a vacuum.

As an alternative to this aqueous working up, the reaction mixture canbe mixed with dichloromethane, separated from the precipitating salts byfiltration and the filtrate concentrated by evaporation in a vacuum.

Independently of the working-up method, the residue is purified bycrystallization or column chromatography on silica gel.

General Operating Instructions 9:

Saponification of Carboxylic Acid Alkyl Esters

0.77 mmol of the carboxylic acid alkyl ester is dissolved in 5 ml ofmethanol and 5 ml of tetrahydrofuran, and it is mixed with 5 ml of a0.5N aqueous lithium or sodium hydroxide solution. After 2-12 hours ofstirring, it is concentrated by evaporation in a vacuum to a very largeextent, neutralized by the addition of aqueous hydrochloric acid andextracted with ethyl acetate. It is dried on sodium sulfate andconcentrated by evaporation in a vacuum. The residue is purified, ifnecessary, by column chromatography on silica gel.

General Operating Instructions 10:

Esterification of Carboxylic Acids

0.2 mmol of carboxylic acid is dissolved in 1 ml of primary or secondaryalcohol, mixed with two drops of concentrated sulfuric acid and stirredfor 12 hours at 60° C. The batch is then mixed with saturated potassiumbicarbonate solution, diluted with water and extracted three times withethyl acetate. After the combined extracts are washed with saturatedsodium chloride solution and dried on sodium sulfate, it is concentratedby evaporation in a vacuum, and the residue is crystallized fromdiisopropyl ether.

General Operating Instructions 11:

Reduction of Carboxylic Acid Alkyl Esters with Lithium Aluminum Hydride

0.15 mmol of carboxylic acid ester is dissolved in tetrahydrofuran andmixed with 0.09 mmol of lithium aluminum hydride. It is allowed to stirfor 1-48 hours, mixed with water and extracted three times withdichloromethane. After the combined organic phases are dried on sodiumsulfate, it is concentrated by evaporation in a vacuum. The residue ispurified, if necessary, by crystallization or by column chromatographyon silica gel.

General Operating Instructions 12:

Wittig Reaction of Benzimidazole Carbaldehydes with(ω-Carboxyalkyl)Triphenylphosphonium Bromides and Esterification withMethanol

2 mmol of the (ω-carboxyalkyl)triphenylphosphonium bromide is mixed in2.5 ml of dimethyl sulfoxide and 2.5 ml of tetrahydrofuran at 0° C. with4 mmol of potassium-tert-butylate, and it is stirred for 30 minutes atT>10° C. Then, a solution of 0.67 mmol of the aldehyde in 2 ml oftetrahydrofuran is added, and it is stirred for 3 hours at 20° C. Thebatch is then mixed with saturated ammonium chloride solution, dilutedwith water and extracted three times with ethyl acetate. After thecombined organic phases are dried on sodium sulfate, it is concentratedby evaporation in a vacuum. The residue is dissolved in 15 ml ofmethanol, mixed with two drops of concentrated sulfuric acid and allowedto stand for 48-72 hours. After concentration by evaporation in avacuum, the residue is purified by column chromatography on silica gel.

General Operating Instructions 13:

Reaction of Aminobenzimidazoles with Alkyl- and Arylsulfonic AcidHalides

47 μmol of aminobenzimidazole derivative is dissolved in 0.5 ml ofdichloromethane, mixed with 51 μmol of triethylamine and 51 μmol ofalkyl- or arylsulfonic acid halide, and the reaction mixture is stirredfor 2-15 hours. For working-up, saturated sodium bicarbonate solution isadded, extracted three times with dichloromethane, the combined organicphases are washed with water, dried on sodium sulfate and concentratedby evaporation in a vacuum. The residue is purified by crystallizationor by column chromatography on silica gel.

General Operating Instructions 14:

Copper-Mediated O- or N-Arylation of Benzimidazoles

5 mmol of an N-unsubstituted benzimidazole derivative or anN-aryl-substituted hydroxybenzimidazole derivative is dissolved in 20 mlof dichloromethane. 10 mmol of an arylboronic acid, 5 mmol of anhydrouscopper(II) acetate, 10 mmol of pyridine or triethylamine and about 2.5 gof molecular sieve (4) are added, stirred for 48-72 hours in amoisture-free environment, then silica gel is added, it is evaporated tothe dry state in a vacuum, and the remaining powder is purified bychromatography on silica gel. Regioisomeric N-arylation products areseparated, if necessary, using HPLC.

General Operating Instructions 15:

Base-Catalyzed N-Substitution of Benzimidazoles

5 mmol of an N-unsubstituted benzimidazole derivative is dissolved in 20ml of dimethylacetamide. 25 mmol of sodium hydride and 20 mmol of anelectron-free aryl or heteroaryl halide are added and refluxed for 48-72hours in a moisture-free environment, then silica gel is added, it isevaporated to the dry state in a vacuum, and the remaining powder ispurified by chromatography on silica gel. Regioisomeric N-arylationproducts are separated, if necessary, using HPLC.

General Operating Instructions 16:

Cyclization to Benzimidazoles with Aldehydes

1 mmol of a 1,2-diaminobenzene derivative is dissolved in 3 ml ofnitrobenzene. 1 mmol of an aryl- or heteroaryl aldehyde is added tothis. It is heated for 2-6 hours to 150° C. and allowed to cool. Theresidue is directly purified by column chromatography on silica gelwithout further working-up.

General Operating Instructions 17:

Conversion of Carboxylic Acids into Carboxylic Acid Amides

0.25 mmol of a carboxylic acid is dissolved in 3 ml ofN,N-dimethylformamide, mixed with 0.38 mmol of a primary or secondaryamine, 0.5 mmol of triethylamine and 0.25 mmol ofdiphenylphosphorylazide, and the mixture is stirred for 2 days. Forworking-up, water is added, it is extracted three times with ethylacetate, the combined organic phases are washed with water, dried onsodium sulfate and concentrated by evaporation in a vacuum. The residueis purified by column chromatography on silica gel.

General Operating Instructions 18:

Conversion of Carboxylic Acid Esters into Carboxylic Acid Amides

0.36 mmol of an amine is dissolved in 3 ml of toluene and mixed drop bydrop with 0.18 ml of a 2 M solution of trimethylaluminum in toluenewhile being cooled in an ice bath. It is mixed with a solution thatconsists of 0.33 mmol of the carboxylic acid methyl ester in 3 ml oftoluene and stirred for 2-8 hours at 95° C. For working-up, water isadded after cooling, extracted three times with ethyl acetate, thecombined organic phases are washed with saturated sodium chloridesolution, dried on sodium sulfate and concentrated by evaporation in avacuum. The residue is purified by column chromatography on silica gel.

EXAMPLE 1 [(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]acetic acid isopropylester

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole(Benincori, T.; Sannicolo, F.; J. Heterocycl. Chem.; 25; 1988;1029-1033) with bromoacetic acid isopropyl ester according to generaloperating instructions 8.

Flash point 137-138° C.

EXAMPLE 2 [(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]ethan-1-ol

was obtained by reaction of[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]acetic acid methyl ester (DE4330959) according to general operating instructions 11.

¹H-NMR (D₆-DMSO): δ=3.72 ppm t (J=7.5 Hz, 2H); 4.02 t (J=7.5 Hz, 2H);6.72 d (J=2 Hz, 1H); 7.10 dd (J=8, 2 Hz, 1H); 7.38-7.68 m (10H); 7.76 d(J=8 Hz, 1H).

EXAMPLE 3 3-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]propan-1-ol

0.5 g of 1,2-diphenyl-6-hydroxy-1H-benzimidazole was reacted accordingto general operating instructions 8 with3-(bromopropoxy)-tert-butyldimethylsilane. After chromatography onsilica gel, it was taken up in 2.5 ml of methanol, 0.4 ml ofconcentrated-hydrochloric acid was added, and it was allowed to stir for2 hours at 20° C. It was poured onto saturated aqueous sodiumbicarbonate solution, extracted three times with ethyl acetate, thecombined extracts were washed with saturated aqueous sodium chloridesolution, dried on sodium sulfate and concentrated by evaporation in avacuum.

Flash point 191-193° C.

EXAMPLE 4 3-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]propanoic acid

100 mg of 3-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]propan-1-ol wasintroduced into 2.5 ml of acetone and mixed at −15° C. with 0.15 ml of asolution of Jones reagent (produced from 0.27 g of chromium(VI) oxide, 1ml of water and 0.23 ml of concentrated sulfuric acid). After 3.5 hoursof stirring at −15° C., it was quenched with the addition ofisopropanol. It was diluted with water, extracted three times withdichloromethane, the combined organic phases were dried on sodiumsulfate and concentrated by evaporation in a vacuum. The residue waspurified by chromatography on silica gel.

¹H-NMR (D₆-DMSO): δ=2.60 ppm t (J=7.5 Hz, 2H), 4.15 t (J=7.5 Hz, 2H);6.64 d (J=2 Hz, 1H); 6.95 dd (J=8, 2 Hz, 1H); 7.30-7.61 m (10H); 7.69 d(J=8 Hz, 1H).

EXAMPLE 5 3-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]propanoic acidmethyl ester

45 mg of 3-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]propanoic acid wasdissolved in 0.5 ml of N,N-dimethylformamide and mixed with 41 mg ofcesium carbonate and 10 μl of methyl iodide. It was allowed to stir for2 days, diluted with dichloromethane, filtered, the filtrate wasconcentrated by evaporation in a vacuum, and the residue waschromatographed on silica gel.

Flash point 120-121° C.

EXAMPLE 6 2-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]propanoic acidmethyl ester

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with2-bromopropanoic acid methyl ester according to general operatinginstructions 8.

Flash point 132-135° C.

EXAMPLE 7 4-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]butanoic acidisopropyl ester

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with4-bromobutanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 89-91° C.

EXAMPLE 8 4-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]butan-1-ol

was obtained by reaction of4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]butanoic acid methyl esteraccording to general operating instructions 11.

Flash point 159-160° C.

EXAMPLE 9 Aceticacid-[4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]but-1-yl]ester

50 mg of 4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]butan-1-ol wasdissolved in 1 ml of dichloromethane, mixed with 0.34 ml of pyridine and20 μl of acetyl chloride and stirred for 15 hours. It was mixed withsaturated sodium bicarbonate solution, diluted with water, extractedtwice with dichloromethane, the combined organic phases were washed withsaturated sodium chloride solution, dried on sodium sulfate andconcentrated by evaporation in a vacuum. The residue was purified usingthick-layer chromatography.

Flash point 68-69° C.

EXAMPLE 10 Pivalicacid-[4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]but-1-yl]-ester

was produced analogously to the instructions, indicated in Example 9,from 50 mg of 4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]butan-1-ol, 0.34ml of pyridine and 22 μl of trimethylacetic acid chloride.

Flash point 104-106° C.

EXAMPLE 114-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]butyl-N-methylcarbamate

100 mg of 4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]butan-1-ol wasdissolved in 4 ml of dichloromethane, mixed with 0.1 ml of triethylamineand 20 mg of methyl isocyanate and stirred for 15 hours. Another 0.1 mlof triethylamine and 20 mg of methyl isocyanate were added, allowed tostir for 20 hours, and then concentrated by evaporation in a vacuum. Theresidue was purified using chromatography on silica gel.

Flash point 124-126° C.

EXAMPLE 12 5-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]pentanoic acidisopropyl ester 994

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with5-bromopentanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 91-92° C.

EXAMPLE 13 6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidmethyl ester

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.44-1.56 m (2H); 1.64-1.85 m (4H); 2.33 t (J=7.5 Hz,2H); 3.66 s (3H); 3.93 t (J=7.5 Hz, 2H); 6.70 d (J=2 Hz, 1H); 6.96 dd(J=8, 2 Hz, 1H); 7.22-7.38 m (5H); 7.43-7.58 m (5H); 7.76 d (J=8 Hz,1H).

EXAMPLE 14 6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.22 ppm d (J=7.5 Hz, 6H); 1.43-1.56 m (2H); 1.62-1.87m (4H); 2.30 t (J=7.5 Hz, 2H); 3.93 t (J=7.5 Hz, 2H), 5.01 sp (J=7.5 Hz,1H); 6.69 d (J=2 Hz, 1H); 6.96 dd (J=8, 2 Hz, 1H); 7.25-7.38 m (5H);7.43-7.55 m (5H); 7.75 d (J=8 Hz, 1H).

EXAMPLE 15 6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acid

was obtained by reaction of6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acid methyl esteraccording to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.35-1.49 ppm m (2H); 1.50-1.63 m (2H); 1.65-1.77 m(2H); 2.23 t (J=7.5 Hz, 2H); 3.92 t (J=7.5 Hz, 2H); 6.62 d (J=2 Hz, 1H);6.95 dd (J=10, 2 Hz, 1H); 7.30-7.62 m (10H); 7.68 d (J=10 Hz, 1H).

EXAMPLE 16 6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]hexan-1-ol

was obtained by reaction of6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acid methyl-esteraccording to general operating instructions 11.

¹H-NMR (CDCl₃): δ=1.35-1.85 ppm m (8H); 3.67 t (J=7.5 Hz, 2H); 3.98 t(J=7.5 Hz, 2H); 6.70 d (J=2 Hz, 1H); 6.98 dd (J=8.2 Hz, 1H); 7.24-7.38 m(5H); 7.45-7.58 m (5H); 7.75 d (J=8 Hz, 1H).

EXAMPLE 17 6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide a)6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]hexanonitrile

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with6-bromohexanonitrile according to general operating instructions 8.

Flash point 108-112° C.

6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

18 mg of potassium carbonate and 40 μl of 30% hydrogen peroxide solutionwere added to a solution of 50 mg of6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanonitrile in 1 ml ofmethanol, and it was allowed to stir for 24 hours. Then, ice-coldaqueous sodium thiosulfate solution was stirred in and extracted threetimes with ethyl acetate. After drying on sodium sulfate, it wasconcentrated by evaporation in a vacuum, and the residue waschromatographed on silica gel.

¹H-NMR (CDCl₃): δ=1.48-1.60 ppm m (2H); 1.65-1.87 m (4H); 2.25 t (J=7.5Hz, 2H); 3.94 t (J=7.5 Hz, 2H); 5.30-5.53 broad (2H), 6.68 d (J=2 Hz,1H); 6.95 dd (J=8, 2 Hz, 1H); 7.23-7.38 m (5H); 7.42-7.58 m (5H), 7.75 d(J=8 Hz, 1H).

EXAMPLE 18 N-Methoxy-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid amide

100 mg of 6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acid wasdissolved in 2 ml of tetrahydrofuran, mixed with 39 mg ofcarbonyldiimidazole, stirred for 30 minutes at 20° C. and then refluxedfor 30 minutes. At 20° C., 21 mg of O-methylhydroxyaminohydrochloridewas then added, and it was allowed to stir for 18 hours. The reactionmixture was diluted with ethyl acetate and washed with 2N aqueoushydrochloric acid and saturated potassium bicarbonate solution. Afterdrying on sodium sulfate, it was concentrated by evaporation in avacuum, and the residue was chromatographed on silica gel.

Flash point 144-145° C.

EXAMPLE 19N-(Phenylmethoxy)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was obtained by reaction of6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acid withO-benzylhydroxylaminohydrochloride according to the general operatinginstructions that are indicated in Example 18.

Flash point 144° C.

EXAMPLE 20N-Hydroxy-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

23 mg ofN-(phenylmethoxy)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamidewas dissolved in 4 ml of ethanol, mixed with 15 mg of palladium oncarbon (10%) and stirred under a hydrogen atmosphere for 3 hours. Aftercatalyst was separated out, it was concentrated by evaporation in avacuum, and the residue was crystallized from diethyl ether.

Flash point 83-85° C.

EXAMPLE 21 7-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]heptanoic acidmethyl ester

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzithidazolewith 7-bromoheptanoic acid methyl ester according to general operatinginstructions 8.

Flash point 77-80° C.

EXAMPLE 22 7-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]heptanoic acid

was obtained by reaction of7-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]heptanoic acid methyl esteraccording to general operating instructions 9.

Flash point 142-145° C.

EXAMPLE 23 7-[(1,2-Diphenyl-3H-benzimidazol-6-yl)oxy]heptanoic acidisopropyl ester

was obtained by reaction of7-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]heptanoic acid withisopropanol according to general operating instructions 10.

Flash point 98-100° C.

EXAMPLE 246-[[1-(3-Nitrophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of6-hydroxy-1-(3-nitrophenyl)-2-phenyl-1H-benzimidazole (DE 4330959) with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 111-113° C.

EXAMPLE 256-[[2-Phenyl-1-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a)(5-Methoxy-2-nitrophenyl)[(3-trifluoromethyl)phenyl]amine

2 g of 3-fluoro-4-nitroanisole and 16 ml of 3-(trifluoromethyl)anilinewere stirred for 72 hours at 140° C. The batch was then diluted withethyl acetate, washed ten times with 4N aqueous hydrochloric acid andonce with saturated sodium chloride solution, dried on sodium sulfate,concentrated by evaporation in a vacuum, and the residue waschromatographed on silica gel.

¹H-NMR (CDCl₃): δ=3.78 ppm s (3H); 6.42 dd (J=8.2 Hz, 1H); 6.60 d (J=2Hz, 1H); 7.45-7.60 m (4H); 8.22 d (J=8 Hz, 1H); 9.78 s (broad)(1H).

b) 6-Methoxy-2-phenyl-1-[(3-trifluoromethyl)phenyl]-1H-benzimidazole

was obtained by hydrogenation of(5-methoxy-2-nitrophenyl)[(3-trifluoromethyl)phenyl]amine according togeneral operating instructions 1 and subsequent cyclization withtriethyl orthobenzoate according to general operating instructions 3.

Flash point 135-137° C.

c) 6-Hydroxy-2-phenyl-1-[(3-trifluoromethyl)phenyl]-1H-benzimidazole

was obtained by reaction of6-methoxy-2-phenyl-1-[(3-trifluoromethyl)phenyl]-1H-benzimidazoleaccording to general operating instructions 6.

¹H-NMR (D₆-DMSO): δ=6.56 ppm d (J=2 Hz, 1H); 6.82 dd (J=8, 2 Hz, 1H);7.32-7.50 m (5H); 7.60 d (J=8 Hz, 1H); 7.70-7.95 m (4H); 9.48 s(broad)(1H).

6-[[2-Phenyl-1-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-hydroxy-2-phenyl-1-[(3-trifluoromethyl)phenyl]-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 106-108° C.

EXAMPLE 266-[[2-Phenyl-1-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid-isopropylester

was obtained by reaction of6-hydroxy-2-phenyl-1[(3-trifluoromethyl)phenyl]-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 113-115° C.

EXAMPLE 276-[[2-Phenyl-1-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[2-phenyl-1-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 9.

Flash point 156-158° C.

EXAMPLE 286-[[2-Phenyl-1-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[2-phenyl-1-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 11.

Flash point 143-145° C.

EXAMPLE 296-[[1-(3-Cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 3-(5-Methoxy-2-nitrophenyl)aminobenzonitrile

2 g of 3-fluoro-4-nitroanisole and 15 ml of 3-aminobenzonitrile werestirred for 65 hours at 140° C. The batch was then diluted with ethylacetate, washed three times with water and once with saturated sodiumchloride solution, dried on sodium sulfate, concentrated by evaporationin a vacuum, and the residue was chromatographed on silica gel.

Flash point 157-158° C.

b) 6-Methoxyl-(3-cyanophenyl)-2-phenyl-1H-benzimidazole

was obtained by hydrogenation of3-(5-methoxy-2-nitrophenyl)aminobenzonitrile according to generaloperating instructions 1 and subsequent cyclization with triethylorthobenzoate according to general operating instructions 3. In thecyclization, tetrahydrofuran, contrary to the general operatinginstructions, was used as a solvent.

Flash point 185-191° C. (decomposition)

c) 6-Hydroxy-1-(3-cyanophenyl)-2-phenyl-1H-benzimidazole

was obtained by reaction of6-methoxyl-(3-cyanophenyl)-2-phenyl-1H-benzimidazole according togeneral operating instructions 7.

Flash point 216-218° C.

6-[[1-(3-Cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-hydroxy-1-(3-cyanophenyl)-2-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 115-118° C.

EXAMPLE 306-[[1-(3-Cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of6-hydroxy-1-(3-cyanophenyl)-2-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 101-102° C.

EXAMPLE 316-[[1-(3-Cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[1-(3-cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl-ester according to general operating instructions 9.

Flash point 99-101° C.

EXAMPLE 326-[[1-(4-Cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 4-(5-Methoxy-2-nitrophenyl)aminobenzonitrile

2 g of 3-fluoro-4-nitroanisole and 15 ml of 4-aminobenzonitrile werestirred for 22 hours at 140° C. The batch was then diluted with ethylacetate, washed three times with 2N aqueous hydrochloric acid, threetimes with water and once with saturated sodium chloride solution, driedon sodium sulfate, concentrated by evaporation in a vacuum, and theresidue was chromatographed on silica gel.

¹H-NMR (CDCl₃): δ=3.70 ppm s (3H); 6.38 dd (J=8, 2 Hz, 1H); 6.68 d (J=2Hz, 1H); 7.27 d (J=8 Hz, 2H); 7.54 d (J=8 Hz, 2H); 8.08 d (J=8 Hz, 1H);9.60 s (broad)(1H).

b) 6-Methoxyl-(4-cyanophenyl)-2-phenyl-1H-benzimidazole

was obtained by hydrogenation of4-(5-methoxy-2-nitrophenyl)aminobenzonitrile according to generaloperating instructions 1 and subsequent cyclization with triethylorthobenzoate according to general operating instructions 3. In thecyclization, tetrahydrofuran, contrary to the general operatinginstructions, was used as a solvent.

¹H-NMR (CDCl₃): δ=3.82 ppm s (3H); 6.72 d (J=2 Hz, 1H); 7.00 dd (J=8.2Hz, 1H); 7.30-7.49 m (7H); 7.78 d (J=8 Hz, 1H); 7.81 d (J=8 Hz, 2H).

c) 6-Hydroxy-1-(4-cyanophenyl)-2-phenyl-1H-benzimidazole

was obtained by reaction of6-methoxy-1-(4-cyanophenyl)-2-phenyl-1H-benzimidazole according togeneral operating instructions 7.

Flash point 266-268° C.

6-[[1-(4-Cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-hydroxy-1-(4-cyanophenyl)-2-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 145-148° C.

EXAMPLE 33-6-[[1-(4-Cyanophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of6-hydroxy-1-(4-cyanophenyl)-2-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 102-103° C.

EXAMPLE 346-[[1-(3-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 1-(3-Chlorophenyl)-6-methoxy-2-phenyl-1H-benzimidazole

was obtained by reduction of(3-chlorophenyl)-(5-methoxy-2-nitrophenyl)amine (Belton, McInerney;Proc. R. Ir. Acad. Sect. B: 69; 1970; 21, 27) according to generaloperating instructions 2 and subsequent cyclization with triethylorthobenzoate according to general operating instructions 3.

Flash point 140-143° C.

b) 1-(3-Chlorophenyl)-6-hydroxy-2-phenyl-1H-benzimidazole

was obtained by reaction of6-methoxy-1-(3-chlorophenyl)-2-phenyl-1H-benzimidazole according togeneral operating instructions 6.

Flash point 210-214° C.

6-[[1-3-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of1-(3-chlorophenyl)-6-hydroxy-2-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 101-105° C.

EXAMPLE 356-[[1-(3-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of1-(3-chlorophenyl)-6-hydroxy-2-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 107-112° C.

EXAMPLE 366-[[1-(3-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[1-(3-chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.36-1.78 ppm m (6H); 2.24 t (J=7.5 Hz, 2H); 3.96 t(J=7.5 Hz, 2H); 6.68 d (J=2 Hz, 1H); 6.97 dd (J=8.2 Hz, 1H); 7.32-7.65 m(9H); 7.69 d (J=8 Hz, 1H).

EXAMPLE 376-[[1-(3-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[1-(3-chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 11.

¹H-NMR (CDCl₃): δ=1.38-1.88 ppm m (8H); 3.67 t (J=7.5 Hz, 2H); 3.96 t(J=7.5 Hz, 2H); 6.70 d (J=2 Hz, 1H); 6.97 dd (J=8, 2 Hz, 1H); 7.18 ddd(J=8, 2, 2 Hz, 1H); 7.25-7.55 m (8H); 7.76 d (J=8 Hz, 1H).

EXAMPLE 386-[[1-(4-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 1-(4-Chlorophenyl)-6-methoxy-2-phenyl-1H-benzimidazole

was obtained by reduction of(4-chlorophenyl)-(5-methoxy-2-nitrophenyl)amine (Kottenhahn et al., J.Org. Chem.; 28; 1963; 3114, 3118) according to general operatinginstructions 2 and subsequent cyclization with triethyl orthobenzoateaccording to general operating instructions 3.

¹H-NMR (CDCl₃) δ=3.82 ppm s (3H); 6.67 d (J=2 Hz, 1H); 6.97 dd (J=8, 2Hz, 1H); 7.22-7.40 m (5H); 7.46-7.55 m (4H); 7.77 d (J=8 Hz, 1H).

b) 1-(4-Chlorophenyl)-6-hydroxy-2-phenyl-1H-benzimidazole

was obtained by reaction of6-methoxy-1-(4-chlorophenyl)-2-phenyl-1H-benzimidazole according togeneral operating instructions 6.

¹H-NMR (D₆-DMSO): δ=6.60 ppm d (J=2 Hz, 1H); 6.87 dd (J=8, 2 Hz, 1H);7.40-7.56 m (7H); 7.64 d (J=8 Hz, 1H); 7.70 d (J=8 Hz, 2H); 9.50 s(broad)(1H).

6-[[1-(4-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of1-(4-chlorophenyl)-6-hydroxy-2-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 100-104° C.

EXAMPLE 396-[[1-(4-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of1-(4-chlorophenyl)-6-hydroxy-2-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 83-88° C.

EXAMPLE 406-[[1-(4-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[1-(4-chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.35-1.78 ppm m (6H); 2.25 t (J=7.5 Hz, 2H); 3.94 t(J=7.5 Hz, 2H); 6.68 d (J=2 Hz, 1H); 6.95 dd (J=8, 2 Hz, 1H); 7.33-7.54m (7H); 7.63 d (J=8 Hz, 2H); 7.69 d (J=8 Hz, 1H).

EXAMPLE 416-[[1-(4-Chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[1-(4-chlorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 11.

Flash point 115-120° C.

EXAMPLE 426-[[1-(2-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 5-Chloro-2-nitrophenyl-o-tolylamine

81 ml of o-toluidine was added to absolution of 10 g of1-chloro-3,4-dinitrobenzene in 50 ml of ethanol, and it was refluxed for72 hours. It was concentrated by evaporation in a vacuum, the residuewas taken up in ethyl acetate and 2N aqueous hydrochloric acid. Theorganic phase was extracted three more times with 2N aqueoushydrochloric acid, dried on sodium sulfate and concentrated byevaporation in a vacuum. The residue was purified by chromatography onsilica gel.

¹H-NMR (CDCl₃): δ=2.28 ppm s (3H); 6.70 dd (J=10, 2 Hz, 1H); 6.80 d (J=2Hz, 1H); 7.22-7.40 m (4H); 8.18 d (J=10 Hz, 1H); 9.40 s (broad)(1H).

b) 5-Methoxy-2-nitrophenyl-o-tolylamine

1 g of 5-chloro-2-nitrophenyl-o-tolylamine was added to a solution of 1g of sodium in 20 ml of methanol, and it was refluxed for 72 hours.Then, it is cooled to 0° C., and the crystalline product is suctionedoff.

¹H-NMR (CDCl₃): δ=2.30 ppm s (3H); 3.72 s (3H); 6.19 d (J=2 Hz, 1H);6.32 dd (J=10, 2 Hz, 1H); 7.20-7.40 m (4H); 8.20 d (J=10 Hz, 1H); 9.62 s(broad)(1H).

c) 6-Methoxy-1-(2-methylphenyl)-2-phenyl-1H-benzimidazole

was obtained by reaction of 5-methoxy-2-nitrophenyl-o-tolylamineaccording to general operating instructions 1 and subsequent cyclizationwith triethyl orthobenzoate according to general operating instructions3.

¹H-NMR (CDCl₃): δ=1.93 ppm s (3H); 3.78 s (3H); 6.42 d (J=2 Hz, 1H);6.97 dd (J=8, 2 Hz, 1H); 7.22-7.48 m (7H); 7.57 dd (J=8, 1 Hz, 2H); 7.78d (J=8 Hz, 1H).

6-[[1-(2-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

6-Methoxy-1-(2-methylphenyl)-2-phenyl-1H-benzimidazole was reactedaccording to general operating instructions 6. The crude product wasreacted with 6-bromohexanoic acid methyl ester according to generaloperating instructions 8.

¹H-NMR (CDCl₃): δ=1.43-1.58 ppm m (2H); 1.62-1.84 m (4H); 1.93 s (3H);2.34 t (J=7.5 Hz, 2H); 3.68 s (3H); 3.90 t (J=7.5 Hz, 2H); 6.42 d (J=2Hz, 1H); 6.96 dd (J=8, 2 Hz, 1H); 7.22-7.48 m (7H); 7.56 dd (J=8, 1.5Hz, 2H); 7.76 d (J=8 Hz, 1H).

EXAMPLE 436-[[1-(2-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[1-(2-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

Flash point 198-200° C.

EXAMPLE 446-[[1-(3-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 5-Chloro-2-nitrophenyl-m-tolylamine

81 ml of m-toluidine is added to a solution of 50 g of1-chloro-3,4-dinitrobenzene in 250 ml of ethanol, and the solution wasallowed to stand for 72 hours. The reaction mixture was filtered, andthe crystallizate was washed with cold ethanol and 2N aqueoushydrochloric acid. It was purified by chromatography on silica gel.

¹H-NMR (CDCl₃): δ=2.40 ppm s (3H); 6.72 dd (J=10, 2 Hz, 1H); 7.04-7.13 m(3H); 7.14 d (J=2 Hz, 1H), 7.32 t (J=10 Hz, 1H); 8.18 d (J=10 Hz, 1H);9.52 s (broad)(1H).

b) 5-Methoxy-2-nitrophenyl-m-tolylamine

39 g of 5-chloro-2-nitrophenyl-m-tolylamine was added to a solution of 9g of sodium in 670 ml of methanol, and it was refluxed for 72 hours.Then, it is cooled to 0° C., and the crystalline product is suctionedoff.

¹H-NMR (CDCl₃): δ=2.40 ppm s (3H); 3.73 s (3H); 6.33 dd (J=10, 2 Hz,1H); 6.58 d (J=2 Hz, 1H); 7.03-7.15 m (3H); 7.31 t (J=10 Hz, 1H); 8.19 d(J=10 Hz, 1H); 9.72 s (broad)(1H).

c) 6-Methoxy-1-(3-methylphenyl)-2-phenyl-1H-benzimidazole

was obtained by reaction of 5-methoxy-2-nitrophenyl-m-tolylamineaccording to general operating instructions 1 and subsequent cyclizationwith triethyl orthobenzoate according to general operating instructions3.

¹H-NMR (CDCl₃): δ=2.42 ppm s (3H); 3.81 s (3H); 6.69 d (J=2 Hz, 1H);7.03 dd (J=8, 2 Hz, 1H); 7.10-7.18 m (2H); 7.30-7.48 m (5H); 7.62 dd(J=8, 1 Hz, 2H); 7.89 d (J=8 Hz, 1H).

d) 6-Hydroxy-1-(3-methylphenyl)-2-phenyl-1H-benzimidazole

was obtained by reaction of6-methoxy-1-(3-methylphenyl)-2-phenyl-1H-benzimidazole according togeneral operating instructions 6.

¹H-NMR (D₆-DMSO): δ=2.34 ppm s (3H); 6.52 d (J=2 Hz, 1H); 6.80 dd (J=8,2 Hz, 1H); 7.15 d (J=8 Hz, 1H); 7.28 s (broad)(1H); 7.32-7.55 m (7H);7.59 d (J=8 Hz, 1H); 9.37 s (broad)(1H).

6-[[1-(3-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-hydroxy-1-(3-methylphenyl)-2-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.44-1.58 ppm m (2H); 1.64-1.85 m (4H); 2.35 t (J=7.5Hz, 2H); 2.40 s (3H); 3.68 s (3H); 3.95 t (J=7.5 Hz, 2H); 6.70 d (J=2Hz, 1H); 6.96 dd (J=8, 2 Hz, 1H); 7.10 d (J=8 Hz, 1H); 7.16 S(broad)(2H); 7.25-7.43 m (4H); 7.55 dd (J=8, 1 Hz, 2H); 7.77 d (J=8 Hz,1H).

EXAMPLE 456-[[1-(3-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of6-hydroxy-1-(3-methylphenyl)-2-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropylester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.22 ppm d (J=8 Hz, 6H); 1.44-1.56 m (2H, CH₂);1.64-1.84 m (4H, CH₂); 2.30 t (J=7.5 Hz, 2H); 2.41 s (3H); 3.95 t (J=7.5Hz, 2H); 5.00 sp (J=8 Hz, 1H); 6.68 d (J=2 Hz, 1H); 6.96 dd (J=8, 2 Hz,1H); 7.10 d (J=8 Hz, 1H); 7.14 s (broad)(1H); 7.25-7.41 m (4H); 7.54 dd(J=8, 1 Hz, 2H); 7.75 d (J=8 Hz, 1H).

EXAMPLE 466-[[1-(3-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[1-(3-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.38-1.80 ppm m (6H); 2.23 t (J=7.5 Hz, 2H);3.84-3.93 m (2H); 6.60 d (J=2 Hz, 1H); 6.87 d (broad) (J=8 Hz, 1H); 7.15d (J=8 Hz, 2H); 7.20-7.32 m (4H); 7.42-7.50 m (2H); 7.59 d (J=8 Hz, 1H);7.77 d (J=8 Hz, 1H).

EXAMPLE 476-[[1-(3-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[1-(3-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 11.

¹H-NMR (CDCl₃): δ=1.40-1.85 m (8H); 2.40 s (3H); 3.68 t (J=7.5 Hz, 2H);3.96 t (J=7.5 Hz, 2H); 6.69 d (J=1.5 Hz, 1H); 6.96 dd (J=8, 1.5 Hz, 1H);7.10 d (J=8 Hz, 1H); 7.13 s (broad)(1H); 7.25-7.42 m (5H); 7.54 dd (J=8,1 Hz, 2H); 7.76 d (J=8 Hz, 1H).

EXAMPLE 486-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 5-Chloro-2-nitrophenyl-p-tolylamine

was produced analogously to 5-chloro-2-nitrophenyl-m-tolylamine from1-chloro-3,4-dinitrobenzene and p-toluidine. It was purified bycrystallization.

¹H-NMR (CDCl₃): δ=2.40 ppm s (3H); 6.70 dd (J=10, 2 Hz, 1H), 7.08 d (J=2Hz, 1H); 7.16 d (J=10 Hz, 2H); 7.28 d (J=10 Hz, 2H); 8.18 d (J=10 Hz,1H); 9.50 s (broad)(1H).

b) 5-Methoxy-2-nitrophenyl-p-tolylamine

was produced analogously to 5-methoxy-2-nitrophenyl-m-tolylamine from5-chloro-2-nitrophenyl)-p-tolylamine and sodium methanolate.

¹H-NMR (CDCl₃): δ=2.39 ppm s (3H); 3.72 s (3H); 6.31 dd (J=10, 2 Hz,1H); 6.50 d (J=2 Hz, 1H); 7.19 d (J=10 Hz, 2H); 7.25 d (J=10 Hz, 2H);8.19 d (J=10 Hz, 1H); 9.70 s (broad)(1H).

c) 6-Methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole

was obtained by reaction of 5-methoxy-2-nitrophenyl-p-tolylamineaccording to general operating instructions 1 and subsequent cyclizationwith triethyl orthobenzoate according to general operating instructions3.

¹H-NMR (CDCl₃): δ=2.49 ppm s (3H); 3.80 s (3H); 6.69 d (J=2 Hz, 1H);6.97 dd (J=8, 2 Hz, 1H); 7.20 d (broad)(J=8 Hz, 2H); 7.25-7.36 m (5H);7.53 dd (J=8, 1 Hz, 2H); 7.76 d (J=8 Hz, 1H).

d) 6-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole

was obtained by reaction of6-methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole according togeneral operating instructions 6.

¹H-NMR (D₆-DMSO): δ=2.40 ppm s (3H); 6.50 d (J=2 Hz, 1H); 6.80 dd (J=8,2 Hz, 1H); 7.28 d (J=8 Hz, 2H); 7.32-7.43 m (5H); 7.46-7.52 m (2H); 7.56d (J=8 Hz, 1H); 9.28 s (broad)(1H).

6-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.44-1.58 ppm m (2H); 1.62-1.86 m (4H); 2.34 t (J=7.5Hz, 2H); 2.48 s (3H); 3.68 s (3H); 3.94 t (J=7.5 Hz, 2H); 6.69 d (J=2Hz, 1H); 6.96 dd (J=8, 2 Hz, 1H); 7.19 d (J=8 Hz, 2H); 7.28-7.38 m (5H);7.55 dd (J=8, 1 Hz, 2H); 7.75 d (J=8 Hz, 1H).

EXAMPLE 496-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.22 ppm d (J=7.5 Hz, 6H); 1.44-1.56 m (2H); 1.62-1.85m (4H); 2.30 t (J=7.5 Hz, 2H); 2.47 s (3H); 3.93 t (J=7.5 Hz, 2H); 5.01sp (J=7.5 Hz, 1H); 6.68 d (J=2 Hz, 1H); 6.96 dd (J=8, 2 Hz, 1H); 7.20 d(J=8 Hz, 2H); 7.26-7.36 m (5H); 7.55 dd (J=8, 1 Hz, 2H); 7.75 d (J=8 Hz,1H).

EXAMPLE 506-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

Flash point 186-190° C.

EXAMPLE 516-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 11.

¹H-NMR (CDCl₃): δ=1.38-1.80 m (8H); 2.47 s (3H); 3.65 t (J=7.5 Hz, 2H);3.93 t (J=7.5 Hz, 2H); 6.68 d (J=2 Hz, 1H); 6.97 dd (J=8, 2 Hz, 1H);7.18 d (J=8 Hz, 2H); 7.24-7.37 m (5H); 7.54 dd (J=8, 1 Hz, 2H); 7.75 d(J=8 Hz, 1H).

EXAMPLE 526-[[1-(3,4-Dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a) 3-(3,4-Dimethylphenyl)amino-4-nitrophenol

3 g of 3-fluoro-4-nitrophenol and 6.9 goof 3,4-dimethylaniline weremixed and stirred for 2 hours at 150° C. After cooling, it was dissolvedin dichloromethane and extracted six times with 1N aqueous hydrochloricacid. The organic phase was discarded, and the combined aqueous phaseswere extracted three times with chloroform. The combined extracts weredried on sodium sulfate, concentrated by evaporation in a vacuum, andthe residue was chromatographed on silica gel.

¹H-NMR (CDCl₃/D₆-DMSO): δ=2.18 ppm s (6H); 6.13 dd (J=8, 2 Hz, 1H); 6.36d (J=2 Hz, 1H); 6.90-7.00 m (2H); 7.09 d (J=8 Hz, 1H); 7.93 d (J=8 Hz,1H); 9.50 s (broad)(1H); 10.19 s (broad)(1H).

b) 6-[3-(3,4-Dimethylphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester

was obtained by reaction of 3-(3,4-dimethylphenyl)amino-4-nitrophenolwith 6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.38-1.52 ppm m (2H); 1.59-1.80 m (4H); 2.30 s (6H);2.33 t (J=7.5 Hz, 2H); 3.68 s (3H); 3.87 t (J=7.5 Hz, 2H); 6.28 d (J=8,2 Hz, 1H); 6.48 d (J=2 Hz, 1H); 7.04 d (J=8 Hz, 1H); 7.06 s (broad)(1H);7.18 d (J=8 Hz, 1H); 8.17 d (J=8 Hz, 1H): 9.71 s (broad)(1H).

6-[[1-(3,4-Dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[3-(3,4-dimethylphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester according to general operating instructions 1 and subsequentcyclization with triethyl orthobenzoate according to general operatinginstructions 3.

¹H-NMR (CDCl₃): δ=1.44-1.56 ppm m (2H); 1.62-1.84 m (4H); 2.30 s (3H);2.33 t (J=7.5 Hz, 2H); 2.34 s (3H); 3.68 s (3H); 3.93 t (J=7.5 Hz, 2H);6.67 d (J=2 Hz, 1H); 6.94 dd (J=8, 2 Hz, 1H); 7.03 dd (J=8, 1.5 Hz, 1H);7.09 s (broad)(1H); 7.22-7.35 m (4H); 7.57 dd (J=8, 1.5 Hz, 2H); 7.76 d(J=8 Hz, 1H).

EXAMPLE 536-[[1-(3,4-Dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 9.

Flash point 158-161° C.

EXAMPLE 546-[[1-(3,5-Dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a) 3-(3,5-Dimethylphenyl)amino-4-nitrophenol

5.4 g of 3-fluoro-4-nitrophenol and 4.3 ml of 3,5-dimethylaniline weremixed and stirred for 6 hours at 120° C. After cooling, it was taken upin ethyl acetate and water and extracted three times with 1N aqueoushydrochloric acid. The combined aqueous phases were extracted threetimes with ethyl acetate. The combined organic phases were dried onsodium sulfate, concentrated by evaporation in a vacuum, and the residuewas crystallized.

¹H-NMR (D₆-DMSO): δ=2.30 ppm s (6H); 6.28 dd (J=8, 2 Hz, 1H); 6.49 d(J=2 Hz, 1H); 6.52 d (J=2 Hz, 1H); 6.90 s (broad)(1H); 6.98 s(broad)(2H); 8.04 d (J=8 Hz, 1H); 9.51 s (broad)(1H).

b) 6-[3-(3,5-Dimethylphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester

was obtained by reaction of 3-(3,5-dimethylphenyl)amino-4-nitrophenolwith 6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.40-1.52 ppm m (2H); 1.60-1.80 m (4H); 2.30 t (J=7.5Hz, 2H); 2.32 s (6H); 3.68 s (3H); 3.88 t (J=7.5 Hz, 2H); 6.30 dd (J=8,2 Hz, 1H); 6.52 d (J=2 Hz, 1H); 6.88 s (broad)(1H); 6.91 s (broad)(2H);8.17 d (J=8 Hz, 1H); 9.69 s (broad)(1H).

6-[3-(3,5-Dimethylphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester

was obtained by reaction of6-[3-(3,5-dimethylphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester according to general operating instructions 1 and subsequentcyclization with triethyl orthobenzoate according to general operatinginstructions 3.

Flash point 124-126° C.

EXAMPLE 556-[[1-(3,5-Dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was by reaction of6-[3-(3,5-dimethylphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester according to general operating instructions 9.

Flash point 162-164° C.

EXAMPLE 566-[[1-(3,5-Dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

was by reaction of6-[3-(3,5-dimethylphenyl)amino-4-nitrophenyl]oxyhexanoic acid withisopropanol according to general operating instructions 10.

Flash point 98-101° C.

EXAMPLE 576-[[1-(3-Methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 3-(3-Methoxyphenyl)amino-4-nitrophenol

4 g of 3-fluoro-4-nitrophenol and 9.4 g of m-anisidine were mixed andstirred for 2.5 hours at 150° C. After cooling, it was dissolved indichloromethane and extracted three times with 1N aqueous hydrochloricacid. The organic phase was dried on sodium sulfate, concentrated byevaporation in a vacuum, and the residue was chromatographed on silicagel.

¹H-NMR (CDCl₃): δ=3.83 ppm s (3H); 6.30 dd (J=10, 2 Hz, 1H); 6.57 d (J=2Hz, 1H); 6.70-6.84 m (2H); 6.89 d (broad)(J=10 Hz, 1H); 7.32 t (J=10 Hz,1H); 8.19 d (J=10 Hz, 1H); 9.68 s (broad)(1H); 9.69 s (broad).

b) 6-[3-(3-Methoxyphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester

was obtained by reaction of 3-(3-methoxyphenyl)amino-4-nitrophenol with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.42-1.58 ppm m (2H); 1.60-1.93 m (4H); 2.34 t (J=7.5Hz, 2H); 3.68 s (3H); 3.80 s (3H); 4.03 t (J=7.5 Hz, 2H); 6.32 dd (J=10,2 Hz, 1H); 6.59 d (J=2 Hz, 1H); 6.68-6.84 m (2H); 6.90 d (broad)(J=8 Hz,1H): 7.32 t (J=8 Hz, 1H); 8.19 d (J=10 Hz, 1H); 9.70 s (broad)(1H).

6-[[1-(3-Methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-[3-(3-methoxyphenyl)amino-4-nitrophenyl]oxyhexanoic acid methyl esteraccording to general operating instructions 1 and subsequent cyclizationwith triethyl orthobenzoate according to general operating instructions3.

¹H-NMR (CDCl₃): δ=1.44-1.58 ppm m (2H); 1.62-1.86 m (4H); 2.34 t (J=7.5Hz, 2H); 3.68 s (3H); 3.78 s (3H); 3.95 t (J=7.5 Hz, 2H); 6.71 d (J=1.5Hz, 1H); 6.83 dd (J=1.5, 1.5 Hz, 1H); 6.90 dd (J=8, 1.5 Hz, 1H); 6.94 dd(J=8, 1.5 Hz, 1H); 7.01 dd (J=8, 1.5 Hz, 1H); 7.27-7.36 m (3H); 7.40 t(J=8 Hz, 1H); 7.56 dd (J=8, 2 Hz, 2H); 7.74 d (J=8 Hz, 1H).

EXAMPLE 586-[[1-(3-Methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[1-(3-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

Flash point 149-152° C.

EXAMPLE 596-[[1-(4-Methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 3-(4-Methoxyphenyl)amino-4-nitrophenol

0.16 g of 3-fluoro-4-nitrophenol and 0.37 g of p-anisidine were mixedand stirred for 1.5 hours at 150° C. After cooling, it was dissolved indichloromethane, and extracted twice with 1N aqueous hydrochloric acidand once with saturated sodium chloride solution. The organic phase wasdried on sodium sulfate and concentrated by evaporation in a vacuum.

¹H-NMR (CDCl₃/D₆-DMSO): δ=3.57 ppm s (3H); 6.06 dd (J=10, 2 Hz, 1H);6.18 d (J=2 Hz, 1H); 6.77 d (J=10 Hz, 2H); 7.03 d (J=10 Hz, 2H); 7.89 d(J=10 Hz, 1H); 9.40 s (broad)(1H); 9.80 s (broad).

b) 6-[3-(4-Methoxyphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester

was obtained by reaction of 3-(4-methoxyphenyl)amino-4-nitrophenol with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.38-1.50 ppm m (2H); 1.60-1.80 m (4H); 2.33 t (J=7.5Hz, 2H); 3.67 s (3H); 3.85 t (J=7.5 Hz, 2H); 3.88 s (3H); 6.29 dd (J=10,1.5 Hz, 1H); 6.30 d (J=1.5 Hz, 1H); 6.98 d (J=10 Hz, 2H); 7.20 d (J=10Hz, 2H); 8.18 d (J=10 Hz, 1H); 9.63 s (broad)(1H).

6-[[1-(4-Methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-[3-(4-methoxyphenyl)amino-4-nitrophenyl]oxyhexanoic acid methyl esteraccording to general operating instructions 1 and subsequent cyclizationwith triethyl orthobenzoate according to general operating instructions3.

Flash point 98-102° C.

EXAMPLE 606-[[1-(4-Methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

Flash point 160-165° C.

EXAMPLE 616-[[1-(3,4-Dimethoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a) 3-(3,4-Dimethoxyphenyl)amino-4-nitrophenol

3 g of 3-fluoro-4-nitrophenol and 8.8 g of 3,4-dimethoxyaniline weremixed and stirred for 2 hours at 150° C. After cooling, it was dissolvedin dichloromethane and extracted twice with 1N aqueous hydrochloricacid. The aqueous phase was extracted twice with chloroform, and thecombined chloroform extracts were dried on sodium sulfate andconcentrated by evaporation in a vacuum.

¹H-NMR (D₆-DMSO): δ=3.75 ppm s (3H); 3.78 s (3H); 6.25 dd (J=10, 2 Hz,1H); 6.35 d (J=2 Hz, 1H); 6.88 dd (J=8, 1.5 Hz, 1H); 6.98 d (J=1.5 Hz,1H); 7.05 d (J=8 Hz, 1H); 8.04 d (J=10 Hz, 1H); 9.52 s (broad)(1H);10.72 s (broad).

b) 6-[3-(3,4-Dimethoxyphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester

was obtained by reaction of 3-(3,4-dimethoxyphenyl)amino-4-nitrophenolwith 6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.40-1.52 ppm m (2H); 1.60-1.80 m (4H); 2.32 t (J=7.5Hz, 2H); 3.68 s (3H); 3.85 t (J=7.5 Hz, 2H); 3.88 s (3H); 3.93 s (3H);6.29 dd (J=10, 1.5 Hz, 1H); 6.33 d (J=1.5 Hz, 1H); 6.80 d (J=1.5 Hz,1H); 6.87 dd (J=10, 1.5 Hz, 1H); 6.92 d (J=10 Hz, 1H); 8.18 d (J=10 Hz,1H); 9.68 s (broad)(1H).

6-[[1-(3,4-Dimethoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[3-(3,4-dimethoxyphenyl)amino-4-nitrophenyl]oxyhexanoic acid methylester according to general operating instructions 1 and subsequentcyclization with triethyl orthobenzoate according to general operatinginstructions 3.

Flash point 116-118° C.

EXAMPLE 626-[[1-(3,4-Dimethoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[1-(3,4-dimethoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 9.

Flash point 158-161° C.

EXAMPLE 636-[[1-[3,4-(Methylenedioxy)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a) 3-(3,4-Methylenedioxyphenyl)amino-4-nitrophenol

0.86 g of 3-fluoro-4-nitrophenol and 2.25 g of 3,4-methylenedioxyanilinewere mixed and stirred for 5 hours at 120° C. The raw mixture waschromatographed on silica gel.

¹H-NMR (D₆-DMSO): δ=6.02 ppm s (2H); 6.25 dd (J=10, 2 Hz, 1H); 6.33 d(J=2 Hz, 1H); 6.72 dd (J=8, 1.5 Hz, 1H); 6.87 d (J=1.5 Hz, 1H); 7.65 d(J=10 Hz, 1H); 8.18 d (J=10 Hz, 1H); 9.52 s (broad)(1H).

b) 6-[3-(3,4-Methylenedioxyphenyl)amino-4-nitrophenyl]oxyhexanoic acidmethyl ester

was obtained by reaction of3-(3,4-methylenedioxyphenyl)amino-4-nitrophenol with 6-bromohexanoicacid methyl ester according to general operating instructions 8.

Flash point 108-111° C.

6-[[1-(3,4-Methylenedioxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[3-(3,4-methylenedioxyphenyl)amino-4-nitrophenyl]oxyhexanoic acidmethyl ester according to general operating instructions 1 andsubsequent cyclization with triethyl orthobenzoate according to generaloperating instructions 3.

¹H-NMR (CDCl₃): δ=1.43-1.55 ppm m (2H); 1.65-1.82 m (4H); 2.35 t (J=7.5Hz, 2H); 3.68 s (3H); 3.95 t (J=7.5 Hz, 2H); 6.10 s (2H); 6.65 d (J=1.5Hz, 1H); 6.72-6.83 m (2H); 6.90 d (J=10 Hz, 1H); 6.93 dd (J=10, 1.5 Hz,1H); 7.29-7.38 m (3H); 7.52-7.62 m (2H); 7.72 d (J=10 Hz, 1H).

EXAMPLE 646-[[1-[3,4-(Methylenedioxy)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[1-(3,4-methylenedioxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 9.

Flash point 130° C.

EXAMPLE 656-[[2-Phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a) 3-(3,4,5-Trimethoxyphenyl)amino-4-nitrophenol

3.7 g of 3-fluoro-4-nitrophenol and 4.76 g of 3,4,5-trimethoxyanilinewere mixed and stirred for 10 hours at 100° C. After cooling, it wastaken up in ethyl acetate and water and extracted three times with ethylacetate. The combined organic phases were extracted three times with 1Naqueous hydrochloric acid and once with saturated sodium chloridesolution, dried on sodium sulfate and concentrated by evaporation to avery large extent in a vacuum. The product was digested with diisopropylether.

¹H-NMR (D₆-DMSO): δ=3.70 ppm s (3H); 3.80 s (6H); 6.28 dd (J=10, 2 Hz,1H); 6.53 d (J=2 Hz, 1H); 6.70 s (2H); 8.05 d (J=10 Hz, 1H); 9.50 s(broad)(1H); 10.71 s (broad).

b) 6-[4-Nitro-3-[(3,4,5-trimethoxyphenyl)amino]-phenyl]oxyhexanoic acidmethyl ester

was obtained by reaction of4-nitro-3-[(3,4,5-trimethoxyphenyl)amino]phenol with 6-bromohexanoicacid methyl ester according to general operating instructions 8.

¹H-NMR (CDCl₃): δ=1.40-1.53 ppm m (2H); 1.60-182 m (4H); 2.32 t (J=7.5Hz, 2H); 3.67 s (3H); 3.85 s (6H); 3.88 t (J=7.5 Hz, 2H); 3.90 s (3H);6.30 dd (J=10, 1.5 Hz, 1H); 6.50 d (J=1.5 Hz, 1H); 6.52 s (2H); 8.18 d(J=10 Hz, 1H); 9.68 s (broad)(1H).

6-[[2-Phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[4-nitro-3-[(3,4,5-trimethoxyphenyl)amino]phenyl]oxy-hexanoic acidmethyl ester according to general operating instructions 1 andsubsequent cyclization with triethyl orthobenzoate according to generaloperating instructions 3.

Flash point 128-130° C.

EXAMPLE 666-[[2-Phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 9.

Flash point 198-201° C.

EXAMPLE 676-[[2-Phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

was obtained by reaction of6-[[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid with isopropanol according to general operating instructions 10.

Flash point 98-101° C.

EXAMPLE 686-[[1-[4-(N,N-Dimethylamino)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a)N,N-Dimethyl-N′-(5-chloro-2-nitrophenyl)benzene-1,4-diamine

was produced analogously to 5-chloro-2-nitrophenyl-m-tolylamine from1-chloro-3,4-dinitrobenzene and N,N-dimethyl-p-phenylenediamine.

¹H-NMR (CDCl₃): δ=3.01 ppm s (6H); 6.63 dd (J=10, 2 Hz, 1H); 6.80 d(broad)(J=10 Hz, 2H); 6.97 d (J=2 Hz, 1H); 7.14 d (J=10 Hz, 2H); 8.14 d(J=10 Hz, 1H); 9.42 s (broad)(1H).

b) N,N-Dimethyl-N′-(5-methoxy-2-nitrophenyl)benzene-1,4-diamine

24.9 g of N,N-dimethyl-N′-(5-chloro-2-nitrophenyl)benzene-1,4-diaminewas added to a solution that consists of 8 g of sodium in 200 ml ofmethanol, and the mixture was heated in an autoclave for 9 hours to 120°C. After cooling, crystalline product was suctioned out.

¹H-NMR (CDCl₃): δ=3.00 ppm s (6H); 3.70 s (3H); 6.25 dd (J=10, 2 Hz,1H); 6.34 d (J=2 Hz, 1H); 6.78 d (J=10 Hz, 2H); 7.14 d (J=10 Hz, 2H);8.16 d (J=10 Hz, 1H); 9.67 s (broad)(1H).

c) 6-Methoxy-1-[4-(N,N-dimethylamino)phenyl]-2-phenyl-1H-benzimidazole

was produced by reaction ofN,N-dimethyl-N′-(5-methoxy-2-nitrophenyl)benzene-1,4-diamine accordingto general operating instructions 1, subsequent reaction of the crudediamine with trimethyl orthobenzoate according to general operatinginstructions 3 and subsequent refluxing of the crude product with 6Naqueous hydrochloric acid for 1 hour. After the reaction mixture wasalkalized with aqueous sodium hydroxide solution, it was extracted withethyl acetate, dried on sodium sulfate and concentrated by evaporationin a vacuum.

¹H-NMR (CDCl₃): δ=3.04 ppm s (6H); 3.80 s (3H); 6.68 d (J=2 Hz, 1H);6.78 d (J=10 Hz, 2H); 6.95 dd (J=10, 2 Hz, 1H); 7.17 d (J=10 Hz, 2H);7.25-7.33 m (3H); 7.56-7.64 m (2H); 7.74 d (J=10 Hz, 1H).

d) 6-Hydroxy-1-[4-(N,N-dimethylamino)phenyl]-2-phenyl-1H-benzimidazole

was obtained by reaction of6-methoxy-1-[4-(N,N-dimethylamino)phenyl]-2-phenyl-1H-benzimidazoleaccording to general operating instructions 6.

¹H-NMR (D₆-DMSO): δ=2.98 ppm s (6H); 6.48 d (J=2 Hz, 1H); 6.78 dd (J=10,2 Hz, 1H); 6.83 d (J=10 Hz, 2H); 7.17 d (J=10 Hz, 2H); 7.30-7.38 m (3H);7.50-7.57 m (3H); 9.32 s (broad)(1H).

6-[[1-[4-(N,N-Dimethylamino)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-hydroxy-1-[4-(N,N-dimethylamino)phenyl]-2-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.43-1.57 ppm m (2H); 1.64-1.85 m (4H); 2.33 t (J=7.5Hz, 2H); 3.05 s (6H); 3.67 s (3H); 3.93 t (J=7.5 Hz, 2H); 6.65 d (J=2Hz, 1H); 6.76 d (J=10 Hz, 2H); 6.93 dd (J=10, 2 Hz, 1H); 7.14 d (J=10Hz, 2H); 7.23-7.27 m (3H); 7.62 dd (J=10, 1.5 Hz, 2H); 7.74 d (J=10 Hz,1H).

EXAMPLE 696-[[1-[4-(N,N-Dimethylamino)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[1-[4-(N,N-dimethylamino)phenyl]-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 9.

Flash point 210-213° C.

EXAMPLE 70 6-[[1-(4-Biphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a) 5-Chloro-2-nitrophenyl-4-biphenylamine

was produced analogously to 5-chloro-2-nitrophenyl-m-tolylamine from1-chloro-3,4-dinitrobenzene and 4-biphenylamine. It was purified bychromatography on silica-gel.

¹H-NMR (CDCl₃): δ=6.76 dd (J=10, 2 Hz, 1H); 7.26 d (J=2 Hz, 1H); 7.35 d(J=8 Hz, 1H); 7.32-7.52 m (4H); 7.60-7.72 m (4H); 8.19 d (J=10 Hz, 1H);9.60 s (broad)(1H).

b) 5-Methoxy-2-nitrophenyl-4-biphenylamine

was produced analogously to 5-methoxy-2-nitrophenyl-m-tolylamine from5-chloro-2-nitrophenyl-4-biphenylamine and sodium methanolate.

Flash point 150-154° C.

b) 1-(4-Biphenyl)-6-methoxy-2-phenyl-1H-benzimidazole

was obtained by reaction of 5-methoxy-2-nitrophenyl-4-biphenylamineaccording to general operating instructions 1 and subsequent cyclizationwith triethyl orthobenzoate according to general operating instructions3.

Flash point 140-144° C.

c) 1-(4-Biphenyl)-6-hydroxy-2-phenyl-1H-benzimidazole

was obtained by reaction of1-(4-biphenyl)-6-methoxy-2-phenyl-1H-benzimidazole according to generaloperating instructions 6.

Flash point 312° C.

6-[[1-(4-Biphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of1-(4-biphenyl)-6-hydroxy-2-phenyl-1H-benzimidazole with 6-bromohexanoicacid methyl ester according to general operating instructions 8.

Flash point 106-108° C.

EXAMPLE 71 6-[[1-(4-Biphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[1-(4-biphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.35-1.78 ppm m (6H); 2.20 t (J=7.5 Hz, 2H); 3.96 m(2H); 6.72 d (J=2 Hz, 1H); 6.97 dd (J=10, 2 Hz, 1H); 7.32-7.58 m (10H);7.69 d (J=10 Hz, 1H); 7.80 d (J=8 Hz, 2H); 7.89 d (J=10 Hz, 2H).

EXAMPLE 72 6-[[1-(2-Naphthyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a) 3-(2-Naphthylamino)-4-nitrophenol

3 g of 3-fluoro-4-nitrophenol and 8.2 g of 2-naphthylamine were mixedand stirred for 8 hours at 180° C. The raw mixture was taken up inchloroform and washed with 2N aqueous hydrochloric acid. The organicphase was dried on sodium sulfate and concentrated by evaporation in avacuum. The residue was chromatographed on silica gel.

¹H-NMR (D₆-DMSO): δ=6.02 ppm s (2H); 6.25 dd (J=10, 2 Hz, 1H); 6.33 d(J=2 Hz, 1H); 6.72 dd (J=8, 1.5 Hz, 1H); 6.87 d (J=1.5 Hz, 1H); 7.05 d(J=10 Hz, 1H); 8.18 d (J=10 Hz, 1H); 9.52 s (broad)(1H).

b) 6-[3-(2-Naphthyl)amino-4-nitrophenyl]oxyhexanoic acid methyl ester

was obtained by reaction of 3-(2-naphthylamino)-4-nitrophenol with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.35-1.49 ppm m (2H); 1.60-1.80 m (4H); 2.30 t (J=7.5Hz, 2H); 3.64 s (3H); 3.84 t (J=7.5 Hz, 2H); 6.35 dd (J=10, 2 Hz, 1H);6.62 d (J=2 Hz, 1H); 7.43 dd (J=10, 2 Hz, 1H); 7.48-7.57 m (2H); 7.75 d(J=2 Hz, 1H); 7.78-7.90 m (2H); 7.91 d (J=10 Hz, 1H); 8.21 D (J=10 Hz,1H); 9.92 s (broad)(1H).

6-[[1-(2-Naphthyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-[1-(2-naphthylamino)-4-nitrophenyl]oxyhexanoic acid methyl esteraccording to general operating instructions 1 and subsequent cyclizationwith triethyl orthobenzoate according to general operating instructions3.

Flash point 111-114° C.

EXAMPLE 73 6-[[1-(2-Naphthyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[1-(2-naphthyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

Flash point 170-175° C.

EXAMPLE 746-[[1-(2-Fluorenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 3-(2-Fluorenylamino)-4-nitrophenol

2.17 g of 3-fluoro-4-nitrophenol and 5 g of 2-aminofluorene were mixedand stirred for 9 hours at 140° C. The raw mixture was taken up in ethylacetate and water and washed with 1N aqueous hydrochloric acid. Theaqueous phase was extracted with ethyl acetate, and the combined organicphases were washed three times with 2N aqueous hydrochloric acid andonce with saturated sodium chloride solution, dried on sodium sulfateand concentrated by evaporation in a vacuum. The residue waschromatographed on silica gel.

¹H-NMR (D₆-DMSO): δ=3.96 ppm s (2H); 6.30 dd (J=10, 2 Hz, 1H); 6.52 d(J=2 Hz, 1H); 7.28-7.45 m (3H); 7.57 s (broad)(1H); 7.60 d (J=8 Hz, 1H);7.92 d (J=8 Hz, 1H); 7.98 d (J=8 HZ, 1H); 8.10 d (J=10 Hz, 1H); 9.70 s(1H); 10.80 s (broad)(1H).

b) 6-[3-(2-Fluorenylamino)-4-nitrophenyl]oxyhexanoic acid methyl ester

was obtained by reaction of 3-(2-fluorenylamino)-4-nitrophenol with6-bromohexanonic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.38-1.50 ppm m (2H); 1.58-1.80 m (4H); 2.30 t (J=7.5Hz, 2H); 3.65 s (3H); 3.84 t (J=7.5 Hz, 2H); 3.95 s (2H); 6.31 dd (J=10,2 Hz, 1H); 6.53 d (J=2 Hz, 1H); 7.33 t (J=8 Hz, 2H); 7.42 t (J=8 Hz,1H); 7.47 s (1H); 7.58 d (J=8 Hz, 1H); 7.80 d (J=8 Hz, 1H), 7.83 d (J=8Hz, 1H); 8.21 d (J=10 Hz, 1H); 9.87 s (broad)(1H).

6-[[1-(2-Fluorenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-[3-(2-fluorenyl)amino)-4-nitrophenyl]oxyhexanoic acid methyl esteraccording to general operating instructions 1 and subsequent cyclizationwith triethyl orthobenzoate according to general operating instructions3.

Flash point 125-128° C.

EXAMPLE 756-[[1-Phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a) Ethyl-(3-trifluoromethyl)benzimidate hydrochloride

9.7 ml of 3-(trifluoromethyl)benzonitrile was dissolved in 12 ml ofethanol, and the solution was saturated with HCl gas while being cooledin an ice bath. After 72 hours, precipitated product was suctioned out.The product was washed with diethyl ether.

Flash point 131-133° C. (decomposition)

b) 5-Methoxy-2-nitrophenyldiphenylamine

A solution of 2 g of 3-fluoro-4-nitroanisole in 16 ml of aniline wasstirred for 24 hours at 140° C. After cooling, it was taken up in ethylacetate and extracted with 2N aqueous hydrochloric acid. The organicphase was dried on sodium sulfate and concentrated by evaporation in avacuum. The residue was chromatographed on silica gel.

¹H-NMR (CDCl₃): δ=3.72 ppm s (3H); 6.36 dd (J=10, 2 Hz, 1H); 6.57 d (J=2Hz, 1H); 7.22-7.33 m (3H); 7.44 dd (J=8, 8 Hz, 2H); 8.18 d (J=10 Hz,1H); 9.78 s (broad)(1H).

c) 4-Methoxy-N²-phenyl-o-phenylenediamine

was obtained by reaction of 5-methoxy-2-nitrophenyldiphenylamineaccording to general operating instructions 1.

¹H-NMR (CDCl₃): δ=3.42 ppm s (broad)(2H); 3.72 s (3H); 5.33 s(broad)(1H); 6.56 dd (J=10, 2 Hz, 1H); 6.76 d (J=10 Hz, 1H); 6.79 d (J=2Hz, 1H); 6.82-6.90 m (3H); 7.25 dd (J=8, 8 Hz, 2H)

d) 6-Methoxy-1-phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazole

was obtained by reaction of 4-methoxy-N²-phenyl-o-phenylenediamine withethyl-(3-trifluoromethyl)benzimidate hydrochloride according to generaloperating instructions 4.

Flash point 138-140° C.

e) 6-Hydroxy-1-phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazole

was obtained by reaction of6-methoxy-1-phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazoleaccording to general operating instructions 7.

¹H-NMR (D₆-DMSO): δ=6.60 ppm d (J=2 Hz, 1H); 6.99 dd (J=10, 2 Hz, 1H);7.50-7.89 m (10H).

6-[[1-Phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-hydroxy-1-phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 68-70° C.

EXAMPLE 766-[[1-Phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

was obtained by reaction of6-hydroxy-1-phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 96-98° C.

EXAMPLE 776-[[1-Phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[1-phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.38-1.80 ppm m (6H); 2.27 t (J=7.5 Hz, 2H); 3.98 t(J=7.5 Hz, 2H); 6.70 d (J=2 Hz, 1H); 7.02 dd (J=10, 2 Hz, 1H); 7.48-7.88m (9H); 7.77 d (J=10 Hz, 1H); 11.94 s (broad)(1H).

EXAMPLE 786-[[1-Phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[1-phenyl-2-[3-(trifluoromethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 11.

¹H-NMR (CDCl₃): δ=1.38-1.68 ppm m (6H); 1.75-1.87 m (2H); 3.60-3.72 m(2H); 3.94 t (J=7.5 Hz, 2H); 6.69 d (J=2 Hz, 1H); 6.99 dd (J=10, 2 Hz,1H); 7.25-7.35 m (2H); 7.40 dd (J=8.8 Hz; 1H); 7.50-7.61 m (4H); 7.68 d(broad)(J=8 Hz, 1H); 7.78 d (J=10 Hz, 1H); 7.83 s (broad)(1H).

EXAMPLE 796-[[2-(3-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 2-(3-Chlorophenyl)-6-methoxy-1-phenyl-1H-benzimidazole

was obtained by reaction of 4-methoxy-N²-phenyl-o-phenylenediamine withethyl-3-chlorobenzimidate hydrochloride (produced according to: DeWolfeand Augustine; J. Org. Chem.; 30; 699) according to general operatinginstructions 4.

Flash point 149-151° C.

b) 2-(3-Chlorophenyl)-6-hydroxy-1-phenyl-1H-benzimidazole

was obtained by reaction of2-(3-chlorophenyl)-6-methoxy-1-phenyl-1H-benzimidazole according togeneral operating instructions 7.

Flash point 199-202° C.

6-[[2-(3-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of2-(3-chlorophenyl)-6-hydroxy-1-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 69-72° C.

EXAMPLE 806-[[2-(3-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of2-(3-chlorophenyl)-6-hydroxy-1-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 98-100° C.

EXAMPLE 816-[[2-(3-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[2-(3-chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

Flash point 137-140° C.

EXAMPLE 826-[[2-(3-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[2-(3-chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 11.

¹H-NMR (CDCl₃): δ=1.40-1.70 ppm m (6H); 1.75-1.86 m (2H); 3.67 t (J=7.5Hz, 2H); 3.93 t (J=7.5 Hz, 2H); 6.69 d (J=2 Hz, 1H); 6.99 dd (J=10, 2Hz, 1H); 7.20 dd (J=8.8 Hz,; 1H); 7.26-7.38 m (4H); 7.47-7.58 m (3H);7.60 dd (J=2, 2 Hz, 1H); 7.76 d (J=10 Hz, 1H).

EXAMPLE 836-[[2-(4-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) Ethyl-4-chlorobenzimidate hydrochloride

10 g of 4-chlorobenzonitrile was suspended in 12 ml of ethanol anddissolved by adding diethyl ether. While being cooled in an ice bath, itwas saturated with HCl gas. After 72 hours, precipitated product wassuctioned out. The product was washed with diethyl ether.

Flash point 173-174° C. (decomposition)

a) 2-(4-Chlorophenyl)-6-methoxy-1-phenyl-1H-benzimidazole

was obtained by reaction of 4-methoxy-N²-phenyl-o-phenylenediamine withethyl-4-chlorobenzimidate hydrochloride according to general operatinginstructions 4.

Flash point 162-164° C.

b) 2-(4-Chlorophenyl)-6-hydroxy-1-phenyl-1H-benzimidazole

was obtained by reaction of2-(4-chlorophenyl)-6-methoxy-1-phenyl-1H-benzimidazole according togeneral operating instructions 7.

Flash point 246-250° C.

6-[[2-(4-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of2-(4-chlorophenyl)-6-hydroxy-1-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 86-87° C.

EXAMPLE 846-[[2-(4-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of2-(4-chlorophenyl)-6-hydroxy-1-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 124-126° C.

EXAMPLE 856-[[2-(4-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[2-(4-chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.35-1.48 ppm m (2H); 1.50-1.62 m (2H); 1.64-1.77 m(2H); 2.23 t (J=7.5 Hz, 2H); 3.91 t (J=7.5 Hz, 2H); 6.64 d (J=2 Hz, 1H);6.96 dd (J=10, 2 Hz, 1H); 7.38-7.50 m (6H); 7.52-7.65 m (3H); 7.70 d(J=10 Hz, 1H).

EXAMPLE 866-[[2-(4-Chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[2-(4-chlorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 11.

¹H-NMR (CDCl₃): δ=1.38-1.68 ppm m (6H); 1.74-1.85 m (2H); 3.67 t(broad)(J=7.5 Hz, 2H); 3.94 t (J=7.5 Hz, 2H); 6.68 d (J=2 Hz, 1H); 6.98dd (J=10, 2 Hz, 1H); 7.22-7.35 m (5H); 7.47 d (J=8 Hz; 2H); 7.49-7.59 m(2H); 7.73 d (J=10 Hz, 1H).

EXAMPLE 876-[[2-(3-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 6-Methoxy-2-(3-methylphenyl)-1-phenyl-1H-benzimidazole

was obtained by reaction of 4-methoxy-N²-phenyl-o-phenylenediamine withethyl-3-methylbenzimidate hydrochloride (produced according to: DeWolfeand Augustine; J. Org. Chem.; 30; 699) according to general operatinginstructions 4.

Flash point 156-158° C.

b) 6-Hydroxy-2-(3-methylphenyl)-1-phenyl-1H-benzimidazole

was obtained by reaction of6-methoxy-2-(3-methylphenyl)-1-phenyl-1H-benzimidazole according togeneral operating instructions 7.

¹H-NMR (D₆-DMSO): δ=2.23 ppm s (3H); 6.52 d (J=2 Hz, 1H); 6.80 dd (J=10,2 Hz, 1H); 7.18 s (broad)(3H); 7.35-7.52 m (3H); 7.50-7:63 m (4H); 9.28s (broad)(1H).

6-[[2-(3-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-hydroxy-2-(3-methylphenyl)-1-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 82-84° C.

EXAMPLE 886-[[2-(3-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of6-hydroxy-2-(3-methylphenyl)-1-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.22 ppm d (J=7.5 Hz, 6H); 1.38-1.56 m (2H); 1.62-1.85m (4H); 2.30 t (J=7.5 Hz, 2H); 2.30 s (3H); 3.93 t (J=7.5 Hz, 2H); 5.00sp (J=7.5 Hz, 1H); 6.68 d (J=2 Hz, 1H); 6.95 dd (J=10, 2 Hz, 1H); 7.13 s(broad)(3H); 7.31 dd (J=8, 2 Hz, 2H); 7.42-7.57 m (4H); 7.76 d (J=10 Hz,1H).

EXAMPLE 896-[[2-(3-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[2-(3-methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.35-1.49 ppm m (2H); 1.50-1.63 m (2H); 1.64-1.78 m(2H); 2.22 t (J=7.5 Hz, 2H); 2.24 s (3H); 3.92 t (J=7.5 Hz, 2H); 6.62 d(J=2 Hz, 1H); 6.95 dd (J=10, 2 Hz, 1H); 7.18 s (broad)(3H); 7.37-7.42 m(3H); 7.51-7.65 m (3H); 7.67 d (J=10 Hz, 1H); 11.90 s (broad)(1H).

EXAMPLE 906-[[2-(3-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[2-(3-methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

Flash point 92-94° C.

EXAMPLE 916-[[2-(4-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 6-Methoxy-2-(4-methylphenyl)-1-phenyl-1H-benzimidazole

was obtained by reaction of 4-methoxy-N²-phenyl-o-phenylenediamine withethyl-4-methylbenzimidate hydrochloride (produced according to: DeWolfeand Augustine; J. Org. Chem.; 30; 699) according to general operatinginstructions 4.

Flash point 150-152° C.

b) 6-Hydroxy-2-(4-methylphenyl)-1-phenyl-1H-benzimidazole

was obtained by reaction of6-methoxy-2-(4-methylphenyl)-1-phenyl-1H-benzimidazole according togeneral operating instructions 7.

Flash point 257-264° C.

6-[[2-(4-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-hydroxy-2-(4-methylphenyl)-1-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 99-102° C.

EXAMPLE 926-[[2-(4-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidisopropyl ester

was obtained by reaction of6-hydroxy-2-(4-methylphenyl)-1-phenyl-1H-benzimidazole with6-bromohexanoic acid isopropyl ester according to general operatinginstructions 8.

Flash point 107-109° C.

EXAMPLE 936-[[2-(4-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[[2-(4-methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.33-1.49 ppm m (2H); 1.50-1.62 m (2H); 1.64-1.77 m(2H); 2.22 t (J=7.5 Hz, 2H); 2.30 s (3H); 3.90 t (J=7.5 Hz, 2H); 6.62 d(J=2 Hz, 1H); 6.94 dd (J=10, 2 Hz, 1H); 7.15 d (J=8 Hz, 2H); 7.36 d (J=8Hz, 2H); 7.40 dd (J=8, 1.5 Hz, 2H); 7.52-7.62 m (3H); 7.68 d (J=10 Hz,1H).

EXAMPLE 946-[[2-(4-Methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexan-1-ol

was obtained by reaction of6-[[2-(4-methylphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 11.

Flash point 150-152° C.

EXAMPLE 956-[[1-Phenyl-2-(4-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 6-Methoxy-1-phenyl-2-(4-pyridinyl)-1H-benzimidazole

0.4 g of 4-methoxy-N²-phenyl-o-phenylenediamine was dissolved in 8 ml ofN,N-dimethylformamide, and the solution was mixed with 0.7 g ofethyl-2-ethoxy-1,2-dihydroquinoline-1-carboxylate and 0.34 g ofisonicotinic acid. It was stirred for 16 hours at 100° C., mixed withwater after cooling, extracted three times with ethyl acetate, thecombined organic phases were washed with saturated sodium chloridesolution, dried on sodium sulfate and concentrated by evaporation in avacuum. After chromatographic purification on silica gel, the amide wastaken up in 5 ml of 6N aqueous hydrochloric acid and refluxed for 3hours. After cooling, it was stirred in saturated sodium bicarbonatesolution, extracted three times with ethyl acetate, the combinedextracts were washed with saturated sodium chloride solution, dried onsodium sulfate and concentrated by evaporation in a vacuum.

¹H-NMR (CDCl₃): δ=3.80 ppm s (3H); 6.66 ppm d (J=2 Hz, 1H); 7.02 dd(J=10, 2 Hz, 1H); 7.32-7.38 m (2H); 7.42 dd (J=8, 1.5 Hz, 2H); 7.54-7.62m (3H); 7.79 d (J=10 Hz, 1H); 8.53 d (broad)(J=6 Hz, 2H)

b) 6-Hydroxy-1-phenyl-2-(4-pyridinyl)-1H-benzimidazole

was produced by reaction of6-methoxy-1-phenyl-2-(4-pyridinyl)-1H-benzimidazole according to generaloperating instructions 7.

¹H-NMR (CD₃OD): δ=6.52 ppm d (J=2 Hz, 1H); 6.82 dd (J=10, 2 Hz, 1H);7.28-7.33 m (2H); 7.39 dd (J=8, 1.5 Hz, 2H); 7.49-7.57 m (4H); 8.40 d(broad)(J=6 Hz, 2H).

6-[[1-Phenyl-2-(4-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was produced by reaction of6-hydroxy-1-phenyl-2-(4-pyridinyl)-1H-benzimidazole according to generaloperating instructions 8.

Flash point 100-103° C.

EXAMPLE 966-[[1-Phenyl-2-(4-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid

was produced by reaction of6-[[1-phenyl-2-(4-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

Flash point 160-162° C.

EXAMPLE 97 6-[(1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester

a) 1,2-Diphenyl-6-hydroxy-5-nitro-1H-benzimidazole

b) 1,2-Diphenyl-6-hydroxy-7-nitro-1H-benzimidazole

c) 1,2-Diphenyl-6-hydroxy-5,7-dinitro-1H-benzimidazole

5 g of 1,2-diphenyl-6-hydroxy-1H-benzimidazole was dissolved in 45 ml ofglacial acetic acid and mixed at 10-15° C. drop by drop with a solutionthat consists of 1.67 g of potassium-nitrite in 15 ml of water. It isallowed to stir for 2 hours in an ice bath and then for 2 hours at 20°C., the reaction mixture is concentrated by evaporation in a vacuum andpurified by chromatography on silica gel.

a) ¹H-NMR (CDCl₃): δ=6.83 ppm s (1H); 7.25-7.44 m (5H); 7.52-7.60 m(5H); 8.66 S (1H); 10.78 s (1H).

b) ¹H-NMR (D₆-DMSO): δ=7.05 ppm d (J=10 Hz, 1H); 7.30-7.53 m (10H); 7.82d (J=10 Hz, 1H); 10.83 s (1H).

c) ¹H-NMR (D₆-DMSO): δ=7.32-7.58 ppm m (10H); 8.67 s (1H).

6-[(1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl)oxy]hexanoic acid methylester

was obtained by reaction of1,2-diphenyl-6-hydroxy-5-nitro-1H-benzimidazole with 6-bromohexanoicacid methyl ester according to general operating instructions 8.

Flash point 123° C.

EXAMPLE 98 6-[(1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl)oxy]hexanoicacid isopropyl ester

was obtained by reaction of1,2-diphenyl-6-hydroxy-5-nitro-1H-benzimidazole with 6-bromohexanoicacid isopropyl ester according to general operating instructions 8.

Flash point 115-117° C.

EXAMPLE 99 6-[(1,2-Diphenyl-7-nitro-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester

was obtained by reaction of1,2-diphenyl-6-hydroxy-7-nitro-1H-benzimidazole with 6-bromohexanoicacid methyl ester according to general operating instructions 8.

Flash point 110-112° C.

EXAMPLE 100 6-[(1,2-Diphenyl-7-nitro-1H-benzimidazol-6-yl)oxy]hexanoicacid isopropyl ester

was obtained by reaction of1,2-diphenyl-6-hydroxy-5-nitro-1H-benzimidazole with 6-bromohexanoicacid isopropyl ester according to general operating instructions 8.

Flash point 88° C.

EXAMPLE 101 6-[(7-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester

340 mg of 6-[(1,2-diphenyl-7-nitro-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester was hydrogenated in ethanol with Raney nickel in anautoclave at 50° C. and at normal pressure. After hydrogen absorptionended, catalyst was filtered out and concentrated by evaporation in avacuum.

Flash point 113-115° C.

EXAMPLE 102 6-[(7-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid isopropyl ester

was obtained analogously to the instructions indicated in Example 101 byreaction of 6-[(1,2-diphenyl-7-nitro-1H-benzimidazol-6-yl)oxy]hexanoicacid isopropyl ester.

¹H-NMR (CDCl₃): δ=1.22 ppm d (J=7.5 Hz, 6H); 1.43-1.88 m (6H); 2.30 t(J=7.5 Hz, 2H); 4.04 t (J=7.5 Hz, 2H); 5.00 sp (J=7.5 Hz, 1H); 6.97 d(J=7.5 Hz, 1H); 7.20-7.33 m (4H); 7.42-7.53 m (7H).

EXAMPLE 1036-[(5,7-Dinitro-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidmethyl ester

was obtained by reaction of5,7-dinitro-1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexanoicacid methyl ester according to general operating instructions 8.

Flash point 88-91° C.

EXAMPLE 1046-[(5,7-Dinitro-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester

was obtained by reaction of5,7-dinitro-1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexanoicacid isopropyl ester according to general operating instructions 8.

Flash point 92-93° C.

EXAMPLE 1056-[[5-(Acetylamino)-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 5-Fluoro-2,4-dinitrophenol

0.41 g of 1,3-difluoro-4,6-dinitrobenzene was dissolved in 8 ml of 0.5 Naqueous sodium hydroxide solution and refluxed for 2 hours. Aftercooling, it was diluted with water and extracted three times withdiethyl ether. The aqueous phase was made acidic by adding 1Nhydrochloric acid and extracted with diethyl ether. The organic phasewas dried on sodium sulfate and concentrated by evaporation in a vacuum.

¹H-NMR (CDCl₃): δ=7.10 ppm d (J=12 Hz, 1H); 9.03 d (J=8 Hz, 1H); 11.10 s(1H).

b) 2,4-Dinitro-5-hydroxydiphenylamine

100 μl of aniline was added to the suspension that consists of 50 mg of5-fluoro-2,4-dinitrophenol in 0.5 ml of ethanol, it was stirred for 30minutes and then allowed to stand for 15 hours. It was suctioned off,the solid was washed with 1N aqueous hydrochloric acid and dried in avacuum.

¹H-NMR (CDCl₃): δ=6.58 ppm s (1H); 7.31 d (J=10 Hz, 2H); 7.39 dd (J=10,10 Hz, 1H); 7.51 dd (J=10, 10 Hz, 2H); 9.20 s (1H); 9.90 s (broad)(1H);10.97 s (broad)(1H).

c) Acetic acid-(2,4-dinitro-5-phenylamino)phenyl ester

0.11 ml of acetic acid anhydride was added to 275 mg of2,4-dinitro-5-hydroxydiphenylamine in 1 ml of pyridine, and it wasallowed to stir for 30 minutes in an ice bath and then for 1 more hourat 20° C. After dilution with ethyl acetate, it was washed three timeswith ice-cold 1N aqueous hydrochloric acid, once with saturatedpotassium bicarbonate solution and once with saturated sodium chloridesolution, dried on sodium sulfate and concentrated by evaporation in avacuum.

¹H-NMR (CDCl₃): δ=2.34 ppm s (3H); 6.80 s (1H); 7.32 d (J=10 Hz, 2H);7.40 dd (J=10, 10 Hz, 1H); 7.52 dd (J=10, 10 Hz, 2H); 9.21 s (1H); 9.95s (broad)(1H).

d) Acetic acid-(1,2-diphenyl-6-hydroxy-1H-benzimidazol-5-yl)amide

was obtained by reaction of aceticacid-(2,4-dinitro-5-phenylamino)phenyl ester according to generaloperating instructions 1 and subsequent reaction with trimethylorthobenzoate according to general operating instructions 3.

¹H-NMR (CDCl₃): δ=2.26 ppm s (3H); 6.88 s (1H); 7.22-7.36 m (5H);7.42-7.53 m (5H); 7.61 s (1H); 8.43 s (broad)(1H).

6-[[5-(Acetylamino)-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of aceticacid-(1,2-diphenyl-6-hydroxy-1H-benzimidazol-5-yl)amide with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 128-130° C.

EXAMPLE 106 6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid isopropyl ester

was obtained by reaction of6-[(1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester according to general operating instructions 1.

¹H-NMR (CDCl₃): δ=1.23 ppm d (J=7.5 Hz, 6H); 1.47-1.90 m (6H); 2.32 t(J=7.5 Hz, 2H); 3.95 t (J=7.5 Hz, 2H); 5.02 sp (J=7.5 Hz, 1H); 6.60 s(1H); 7.20 s (1H); 7.22-7.33 m (5H); 7.43-7.58 m (5H).

EXAMPLE 1076-[[5-[[(4-Bromophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester was reacted according to general operating instructions13 with 4-bromobenzenesulfonic acid chloride.

Flash point 173-175° C.

EXAMPLE 108 6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester

was obtained by reaction of6-[(1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl)oxy]hexanoic acid methylester according to general operating instructions 1.

¹H-NMR (CDCl₃): δ=1.48-1.88 ppm (6H); 2.36 t (J=7.5 Hz, 2H, CH₂═CO);3.67 s (3H); 3.94 t (J=7.5 Hz, 2H); 6.60 s (1H); 7.21 s (1H); 7.22-7.35m (5H); 7.43-7.59 m (5H).

EXAMPLE 1096-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acid methylester was reacted according to general operating instructions 13 with4-chlorobenzenesulfonic acid chloride.

Flash point 157-159° C.

EXAMPLE 1106-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester was reacted according to general operating instructions13 with 4-chlorobenzenesulfonic acid chloride.

Flash point 158-159° C.

EXAMPLE 1116-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester according to general operating instructions 9.

Flash point 201-203° C.

EXAMPLE 1126-[[1,2-Diphenyl-5-[[(3-methylphenyl)sulfonyl]amino]-1H-benzimidazol-6-yl]oxy]-hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester was reacted according to general operating instructions13 with 3-methylbenzenesulfonic acid chloride.

Flash point 149-151° C.

EXAMPLE 1136-[[1,2-Diphenyl-5-[[(4-methylphenyl)sulfonyl]amino]-1H-benzimidazol-6-yl]oxy]-hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester was reacted according to general operating instructions13 with 4-methylbenzenesulfonic acid chloride.

Flash point 139-141° C.

EXAMPLE 1146-[[1,2-Diphenyl-5-[[(4-methoxyphenyl)sulfonyl]amino]-1H-benzimidazol-6-yl]oxy]-hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester was reacted according to general operating instructions13 with 4-methoxybenzenesulfonic acid chloride.

¹H-NMR (CDCl₃): δ=1.25 ppm d (J=7.5 Hz, 6H); 1.35-1:45 m (2H); 1.59-1.73m (4H); 2.30 t (J=7.5 Hz, 2H); 3.72 t (J=7.5 Hz, 2H); 3.80 s (3H); 5.02sp (J=7.5 Hz, 1H); 6.50 s (1H); 6.85 d (J=10 Hz, 2H); 6.99 s (1H);7.25-7.35 m (5H); 7.45-7.52 m (5H); 7.74 d (J=10 Hz, 2H); 7.99 s (1H).

EXAMPLE 1156-[[1,2-Diphenyl-5-[[[(4-trifluoromethyl)phenyl]sulfonyl]amino]-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropylester was reacted according to general operating instructions13 with 4-(trifluoromethyl)benzenesulfonic acid chloride.

Flash point 170-171° C.

EXAMPLE 1166-[[5-[[[4-(Acetylamino)phenyl]sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester was reacted according to general operating instructions13 with 4-(acetylamino)benzenesulfonic acid chloride.

Flash point 100-102° C.

EXAMPLE 1176-[[5-[[Bis(3-chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]-hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester was reacted according to general operating instructions13 with 3-chlorobenzenesulfonic acid chloride.

Flash point 163-167° C.

EXAMPLE 1186-[[1,2-Diphenyl-5-[(propylsulfonyl)amino]-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester was reacted according to general operating instructions13 with propanesulfonic acid chloride.

Flash point 126-128° C.

EXAMPLE 1196-[[5-[(Benzylsulfonyl)amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

6-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanoic acidisopropyl ester was reacted with benzenemethanesulfonic acid chlorideaccording to general operating instructions 13.

Flash point 137-138° C.

EXAMPLE 120 4-[(1,2-Diphenyl-1H-benzimidazol-6-yl]oxy]methylbenzoic acidmethyl ester

was produced by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with4-(bromomethyl)-benzoic acid methyl ester according to general operatinginstructions 8.

Flash point 180-184° C.

EXAMPLE 121 4-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]methylbenzoic acid

was produced by reaction of4-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]methylbenzoic acid methylester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=5.12 ppm s (2H); 6.76 d (J=2 Hz, 1H); 7.04 dd (J=10,2 Hz, 1H); 7.30-7.63 m (12H); 7.70 d (J=10 Hz, 1H); 7.89 d (J=8 Hz, 2H).

EXAMPLE 1224-[[1-(3-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]methylbenzoicacid methyl ester

was produced by reaction of6-hydroxy-1-(3-methylphenyl)-2-phenyl-1H-benzimidazole with4-(bromomethyl)benzoic acid methyl ester according to general operatinginstructions 8.

Flash point 138-142° C.

EXAMPLE 1234-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]methylbenzoicacid methyl ester

was produced by reaction of6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole with4-(bromomethyl)benzoic acid methyl ester according to general operatinginstructions 8.

Flash point 145-148° C.

EXAMPLE 124 2-[2-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]aceticacid-tert-butyl ester

0.2 g of [(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]ethan-1-ol wassuspended in 1.7 ml of toluene and 0.7 ml of tetrahydrofuran. 0.1 ml ofbromoacetic acid-tert-butyl ester, 13 mg of tetrabutylammonium hydrogensulfate, and 1.45 ml of 32% sodium hydroxide solution were added to it,and it was allowed to stir for 48 hours. Another 0.1 ml of bromoaceticacid-tert-butyl ester and 13 mg of tetrabutylammonium hydrogen sulfatewere added, and the mixture was left for 48 hours in an ultrasound bath.Then, it was diluted with water and extracted three times with toluene.The combined organic phases were washed with water and saturated sodiumchloride solution, dried on sodium sulfate and concentrated byevaporation in a vacuum. The residue was chromatographed on silica gel.

¹H-NMR (CDCl₃): δ=1.43 ppm s (9H); 3.91 t (J=6 Hz, 2H); 4.10 s (2H);4.17 t (J=6 Hz, 2H); 6.75 d (J=2 Hz, 1H); 7.00 dd (J=10, 2 Hz, 1H);7.24-7.36 m (5H); 7.45-7.56 m (5H); 7.76 d (J=10 Hz, 1H)

EXAMPLE 125 2-[2-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]aceticacid

50 mg of 2-[2-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]aceticacid-tert-butyl ester was dissolved in 0.5 ml of trifluoroacetic acidand stirred for 48 hours. Then, it was diluted with water and extractedthree times with ethyl acetate. The combined organic phases were washedwith saturated sodium chloride solution, dried on sodium sulfate andconcentrated by evaporation in a vacuum. The residue was chromatographedon silica gel.

Flash point 134-136° C.

EXAMPLE 126 2-[2-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]aceticacid methyl ester

35 mg of 2-[2-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]acetic acidwas dissolved in 0.4 ml of N,N-dimethylformamide and mixed with 29 mg ofcesium carbonate and 50 μl of methyl iodide. It was stirred for 20hours, then concentrated by evaporation in a vacuum and chromatographedon silica gel.

¹H-NMR (CDCl₃): δ=3.73 ppm s (3H); 3.93 t (J=6 Hz, 2H); 4.18 t (J=6 Hz,2H); 4.25 s (2H); 6.73 d (J=2 Hz, 1H); 7.00 dd (J=10, 2 Hz, 1H);7.25-7.42 m (5H); 7.46-7.58 m (5H); 7.77 d (J=10 Hz, 1H).

EXAMPLE 1273-[2-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]propanoicacid-tert-butyl ester

0.2 g of [(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]ethan-1-ol wassuspended in 1.7 ml of toluene and 0.7 ml of tetrahydrofuran. 60 μl ofacrylic acid-tert-butyl ester, 13 mg of tetrabutylammonium hydrogensulfate, and 1.45 ml of 32% sodium hydroxide solution were added to it,and it was allowed to stir for 48 hours. Another 60 μl of acrylicacid-tert-butyl ester and 13 mg of tetrabutylammonium hydrogen sulfatewere added, and the mixture was left for 48 hours in an ultrasound bath.Then, it was diluted with water and extracted three times with toluene.The combined organic phases were washed with water and saturated sodiumchloride solution, dried on sodium sulfate and concentrated byevaporation in a vacuum. The residue was chromatographed on silica gel.

¹H-NMR (CDCl₃): δ=1.45 ppm s (9H); 2.52 t (J=8 Hz, 2H); 3.73-3.84 m(4H); 4.10 t (J=6 Hz, 2H); 6.72 d (J=2 Hz, 1H); 6.99 dd (J=10, 2 Hz,1H); 7.22-7.83 m (5H); 7.45-7.57 m (5H); 7.75 d (J=10 Hz, 1H).

EXAMPLE 1283-[2-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]propanoic acid

50 mg of 3-[2-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]propanoicacid-tert-butyl ester was dissolved in 0.5 ml of trifluoroacetic acidand stirred for 15 hours. Then, it was diluted with water and extractedthree times with ethyl acetate. The combined organic phases were washedwith saturated sodium chloride solution, dried on sodium sulfate andconcentrated by evaporation in a vacuum. The residue was chromatographedon silica gel.

¹H-NMR (D₆-DMSO): δ=2.26 ppm t (J=8 Hz, 2H); 3.60-3.70 m (4H); 3.98-4.06m (2H); 6.65 d (J=2 Hz, 1H); 6.94 dd (J=10, 2 Hz, 1H); 7.30-7.62 m(10H); 7.68 d (J=10 Hz, 1H).

EXAMPLE 1293-[2-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]propanoic acidmethyl ester

35 mg of 3-[2-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]propanoicacid was dissolved in 0.4 ml of N,N-dimethylformamide, mixed with 28 mgof cesium carbonate and 50 μl of methyl iodide and stirred for 30 hours.Then, it was diluted with water and extracted three times with ethylacetate. The combined organic phases were washed with saturated sodiumchloride solution, dried on sodium sulfate and concentrated byevaporation in a vacuum. The residue was chromatographed on silica gel.

Flash point 91-93° C.

EXAMPLE 1303-[3-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]propoxy]propanoicacid-tert-butyl ester

0.2 g of 3-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]propan-1-ol wassuspended in 1.7 ml of toluene and 0.7 ml of tetrahydrofuran. 60 μl ofacrylic acid-tert-butyl ester, 13 mg of tetrabutylammonium hydrogensulfate, and 1.47 ml of 32% sodium hydroxide solution were added to it,and it was allowed to stir for 48 hours. Another 60 μl of acrylicacid-tert-butyl ester and 13 mg of tetrabutylammonium hydrogen sulfatewere added, and the mixture was left for 48 hours in an ultrasound bath.Then, it was diluted with water and extracted three times with toluene.The combined organic phases were washed with water and saturated sodiumchloride solution, dried on sodium sulfate and concentrated byevaporation in a vacuum. The residue was chromatographed on silica gel.

Flash point 95-98° C.

EXAMPLE 131 (E/Z)-5-(1,2-Diphenyl-1H-benzimidazol-6-yl)pent-4-enoic acidmethyl ester a) 1,2-Diphenyl-6-methyl-1H-benzimidazole

5.1 g of 5-methyl-2-nitrodiphenylamine was hydrogenated in 55 ml ofethanol according to general operating instructions 1. The crude productwas reacted with trimethyl orthobenzoate according to general operatinginstructions 3.

Flash point 134-136° C.

b) 1,2-Diphenyl-1H-benzimidazole-6-carbaldehyde

1 g of 1,2-diphenyl-6-methyl-1H-benzimidazole was suspended in 31 ml of40% sulfuric acid and mixed with 13.5 g of cerium ammonium nitrate. Itwas allowed to stir for 2.5 hours at 80° C., cooled to 20° C., andcarefully stirred into saturated aqueous sodium bicarbonate solution.The mixture was extracted three times with ethyl acetate, the combinedextracts were washed with saturated aqueous sodium chloride solution,dried on sodium sulfate solution and evaporated to the dry state in avacuum. The residue was chromatographed on silica gel.

¹H-NMR (CDCl₃): δ=7.30-7.42 ppm m (5H); 7.50-7.66 m (5H); 7.81 d (J=2Hz, 1H); 7.89 dd (J=8, 2 Hz, 1H); 8.00 d (J=8 Hz, 1H); 10.05 s (1H).

(E/Z)-5-(1,2-Diphenyl-1H-benzimidazol-6-yl)pent-4-enoic acid methylester

was obtained by reaction of 1,2-diphenyl-1H-benzimidazole-6-carbaldehydeaccording to general operating instructions 12 with3-carboxypropyltriphenylphosphonium bromide.

¹H-NMR (CDCl₃): δ=2.40-2.71 ppm m (4H); 3.68 (3.66) at s (3H) each;5.56-5.64 (6.12-6.22) at m (1H) each; 6.50 d (J=18 Hz, 1H); 6.58 d(broad) (J=12 Hz, 1H); 7.12 (7.15) at s (broad)(1H) each; 7.25-7.40 m(6H); 7.45-7.62 m (5H); 7.80 (7.83) at d (J=8 Hz, 1H) each.

EXAMPLE 132 E-5-(1,2-Diphenyl-1H-benzimidazol-6-yl)pent-4-enoic acid

was obtained by reaction of(E/Z)-5-(1,2-diphenyl-1H-benzimidazol-6-yl)pent-4-enoic acid methylester according to general operating instructions 9.

¹H-NMR (CD₃OD): δ=2.26-2.43 ppm m (4H); 6.10-6.21 m (1H) 6.45 d (J=18Hz, 1H); 7.08 s (1H); 7.22-7.52 m (11H); 7.59 d (J=8 Hz, 1H).

EXAMPLE 133 5-(1,2-Diphenyl-1H-benzimidazol-6-yl)pentanoic acid methylester

was obtained by reaction of(E/Z)-5-(1,2-diphenyl-1H-benzimidazol-6-yl)pent-4-enoic acid methylester according to general operating instructions 1.

¹H-NMR (CDCl₃): δ=1.63-1.72 ppm m (4H); 2.30-2.39 m (2H); 2.68-2.77 m(2H); 3.65 s (3H); 7.04 s (broad)(1H); 7.17 dd (J=8, 2 Hz, 1H);7.25-7.38 m (5H); 7.45-7.60 m (5H); 7.79 d (J=8 Hz, 1H).

EXAMPLE 134 5-(1,2-Diphenyl-1H-benzimidazol-6-yl)pentanoic acid

was obtained by reaction of5-(1,2-diphenyl-1H-benzimidazol-6-yl)pentanoic acid methyl esteraccording to general operating instructions 9.

Flash point 192-193° C.

EXAMPLE 135 (E/Z)-6-(1,2-Diphenyl-1H-benzimidazol-6-yl)hex-5-enoic acidmethyl ester

was obtained by reaction of 1,2-diphenyl-1H-benzimidazole-6-carbaldehydeaccording to general operating instructions 12 with4-carboxybutyltriphenylphosphonium bromide.

¹H-NMR (CDCl₃): δ=1.72-1.88 ppm m (2H); 2.20-2.42 m (4H); 3.65 (3.67) ats (3H, CH₃) each; 5.51-5.68 (6.10-6.20) at m (1H) each; 6.48 d (J=18 Hz,1H); 6.56 d (broad)(J=12 Hz, 1H); 7.12 (7.16) at s (broad)(1H) each;7.25-7.38 m (6H); 7.45-7.60 m (5H); 7.80 (7.84) at d (J=8 Hz, 1H) each.

EXAMPLE 136 (E/Z)-6-(1,2-Diphenyl-1H-benzimidazol-6-yl)hex-5-enoic acid

was obtained by reaction of(E/Z)-6-(1,2-diphenyl-1H-benzimidazol-6-yl)hex-5-enoic acid methyl esteraccording to general operating instructions 9.

¹H-NMR (CDCl₃): δ=1.74-1.89 ppm m (2H); 2.22-2.43 m (4H); 5.58-5.68(6.10-6.22) at m (1H) each; 6.47 d (J=18 Hz, 1H); 6.55 d (broad) (J=12Hz, 1H); 7.11 (7.14) at s (broad)(1H) each; 7.25-7.40 m (6H); 7.48-7.59m (5H); 7.80 (7.85) at d (J=8 Hz, 1H) each.

EXAMPLE 137 6-(1,2-Diphenyl-1H-benzimidazol-6-yl)hexanoic acid methylester

was obtained by reaction of(E/Z)-6-(1,2-diphenyl-1H-benzimidazol-6-yl)hex-5-enoic acid methyl esteraccording to general operating instructions 1.

¹H-NMR (CDCl₃): δ=1.32-1.43 ppm m (2H); 1.62-1.74 m (4H); 2.31 t (J=7.5Hz, 2H); 2.72 t (J=7.5 Hz, 2H); 3.56 s (3H); 7.02 s (broad)(1H); 7.18 dd(J=8, 2 Hz, 1H); 7.27-7.38 m (5H); 7.45-7.60 m (5H); 7.80 d (J=8 Hz,1H).

EXAMPLE 138 6-(1,2-Diphenyl-1H-benzimidazol-6-yl)hexanoic acid

was obtained by reaction of6-(1,2-diphenyl-1H-benzimidazol-6-yl)hexanoic acid methyl esteraccording to general operating instructions 9.

¹H-NMR (CDCl₃): δ=1.30-1.45 ppm m (2H); 1.54-1.74 m (4H); 2.32 t (J=7.5Hz, 2H); 2.70 t (J=7.5 Hz, 2H); 7.02 s (broad)(1H); 7.20 dd (J=8, 2 Hz,1H); 7.25-7.38 m (5H); 7.42-7.60 m (5H); 7.81 d (J=8 Hz, 1H).

EXAMPLE 139 (E/Z)-7-(1,2-Diphenyl-1H-benzimidazol-6-yl)hept-6-enoic acidmethyl ester

was obtained by reaction of 1,2-diphenyl-1H-benzimidazole-6-carbaldehydeaccording to general operating instructions 12 with5-carboxypentyltriphenylphosphonium bromide.

¹H-NMR (CDCl₃): δ=1.43-1.55 ppm m (2H); 1.58-1.72 m (2H); 2.18-2.38 m(4H); 3.65 (3.66) at s (3H, CH₃) each; 5.58-5.68 (6.12-6.22) at m (1H)each; 6.45 d (J=18 Hz, 1H); 6.54 d (broad)(J=12 Hz, 1H); 7.12 (7.14) ats (broad)(1H) each; 7.26-7.40 m (6H); 7.48-7.60 m (5H); 7.80 (7.83) at d(J=8 Hz, 1H) each.

EXAMPLE 140 (E/Z)-7-(1,2-Diphenyl-1H-benzimidazol-6-yl)hept-6-enoic acid

was obtained by reaction of(E/Z)-7-(1,2-diphenyl-1H-benzimidazol-6-yl)hept-6-enoic acid methylester according to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.40-1.60 ppm m (4H); 2.14-2.28 m (4H); 6.18-6.30 m(1H); 6.50 d (J=18 Hz, 1H); 7.07 (7.12) at s (broad)(1H) each; 7.32-7.64m (11H); 7.70 (7.78) at d (J=8 Hz, 1H) each; 12.00 s (broad)(1H).

EXAMPLE 141 7-(1,2-Diphenyl-1H-benzimidazol-6-yl)heptanoic acid methylester

was obtained by reaction of(E/Z)-7-(1,2-diphenyl-1H-benzimidazol-6-yl)hept-6-enoic acid methylester according to general operating instructions 1.

¹H-NMR (CDCl₃): δ=1.30-1.42 ppm m (4H); 1.55-1.70 m (4H); 2.30 t (J=7.5Hz, 2H); 2.68 t (J=7.5 Hz, 2H); 3.56 s (3H); 7.02 s (broad)(1H); 7.18 dd(J=8, 2 Hz, 1H); 7.28-7.35 m (5H); 7.45-7.58 m (5H); 7.79 d (J=8 Hz,1H).

EXAMPLE 142 7-(1,2-Diphenyl-1H-benzimidazol-6-yl)heptanoic acid

was obtained by reaction of7-(1,2-diphenyl-1H-benzimidazol-6-yl)heptanoic acid methyl esteraccording to general operating instructions 9.

Flash point 99-103° C.

EXAMPLE 143 N-(1,2-Diphenyl-1H-benzimidazol-5-yl)benzenesulfonamideEXAMPLE 144N-(Phenylsulfonyl)-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamidea) 5-Amino-1,2-diphenyl-1H-benzimidazole

2,4-Diaminodiphenylamine is reacted with trimethyl orthobenzoateaccording to general operating instructions 3.

¹H-NMR (CDCl₃): δ=6.70 ppm dd (J=7.5, 2 Hz, 1H); 7.06 d (J=7.5 Hz, 1H);7.18 d (J=2 Hz, 1H); 7.28-7.60 m (10H).

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with benzenesulfonicacid chloride according to general operating instructions 13.

143: Flash point 196-205° C.

144: ¹H-NMR (CDCl₃): δ=6.94 ppm dd (J=7.5, 2 Hz, 1H); 7.20 d (J=2 Hz,1H); 7.26-8.04 m (21H).

EXAMPLE 1453-Chloro-N-(1,2-Diphenyl-1H-benzimidazol-5-yl)benzenesulfonamide EXAMPLE146N-[(3-Chlorophenyl)sulfonyl]-N-(1,2-diphenyl-1H-benzimidazol-5-yl)-(3-chlorobenzene)sulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with3-chlorobenzenesulfonic acid chloride according to general operatinginstructions 13.

145: Flash point 160-162° C.

146: ¹H-NMR (CDCl₃): δ=6.93 ppm dd (J=7.5, 2 Hz, 1H); 7.25 d (J=2 Hz,1H); 7.28-7.57 m (13H); 7.66 d (broad)(2H); 7.90 d (broad)(2H); 8.00 d(broad)(2H).

EXAMPLE 1474-Chloro-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with4-chlorobenzenesulfonic acid chloride according to general operatinginstructions 13.

¹H-NMR (CDCl₃): δ=6.86 ppm s (broad)(1H); 7.11 d (J=7.5, 2 Hz, 1H); 7.17d (J=2 Hz, 1H); 7.25-7.55 m (12H); 7.70 d (J=10 Hz, 2H).

EXAMPLE 1484-Bromo-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamide EXAMPLE149N-(4-Bromophenylsulfonyl)-N-(1,2-diphenyl-1H-benzimidazol-5-yl)-4-bromobenzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with4-bromobenzenesulfonic acid chloride according to general operatinginstructions 13.

148: Flash point 135-139° C.

149: ¹H-NMR (CDCl₃): δ=6.90 ppm dd (J=7.5, 2 Hz, 1H); 7.23 d (J=2 Hz,1H); 7.28-7.43 m (11H); 7.72 d (J=10 Hz, 2H); 7.86 d (J=10 Hz, 2H).

EXAMPLE 1504-(Trifluoromethyl)-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamideEXAMPLE 151N-(1,2-Diphenyl-3H-benzimidazol-5-yl)-N-[(3-trifluoromethyl)phenylsulfonyl]-(3-trifluoromethyl)benzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with(3-trifluoromethyl)benzenesulfonic acid chloride according to generaloperating instructions 13.

150: Flash point 116-121° C.

151: Flash point 238-241° C.

EXAMPLE 1523-Methyl-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamide EXAMPLE153N-(1,2-Diphenyl-1H-benzimidazol-5-yl)-N-(3-methylphenylsulfonyl)-3-methylbenzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with3-methylbenzenesulfonic acid chloride according to general operatinginstructions 13.

152: Flash point 192-195° C.

153: Flash point 173-176° C.

EXAMPLE 1544-Methyl-N-(1,2-Diphenyl-1H-benzimidazol-5-yl)benzenesulfonamide EXAMPLE155N-(1,2-Diphenyl-1H-benzimidazol-5-yl)-N-(4-methylphenylsulfonyl)-4-methyl-benzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with4-methylbenzenesulfonic acid chloride according to general operatinginstructions 13.

154: ¹H-NMR (CDCl₃): δ=2.38 ppm s (3H); 6.77 s (broad)(1H); 7.14-7.55 m(14H); 7.66 d (J=10 Hz, 2H).

155: Flash point 234-236° C.

EXAMPLE 1564-Methoxy-N-(1,2-Diphenyl-1H-benzimidazol-5-yl)benzenesulfonamideEXAMPLEN-(1,2-Diphenyl-1H-benzimidazol-5-yl)-N-(4-methoxyphenylsulfonyl)-4-methoxybenzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with4-methoxybenzenesulfonic acid chloride according to general operatinginstructions 13.

156: ¹H-NMR (CDCl₃): δ=3.82 ppm s (3H); 6.78 s (broad)(1H, H-4); 6.88 d(J=7.5 Hz, 1H); 7.14 d (J=1.5 Hz, 1H); 7.28-7.55 m (12H); 7.72 d (J=8Hz, 2H).

157: ¹H-NMR (CDCl₃): δ=3.90 ppm s (6H); 6.93 dd (J=7.5, 2 Hz, 1H); 7.00d (J=10 Hz, 4H); 7.06 d (J=2 Hz, 1H); 7.30-7.58 m (11H); 7.93 d (J=10Hz, 4H).

EXAMPLE 158 N-(1,2-Diphenyl-1H-benzimidazol-5-yl)propanesulfonamideEXAMPLE 159N-(1,2-Diphenyl-1H-benzimidazol-5-yl)-N-(propylsulfonyl)-propanesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted withpropanebenzenesulfonic acid chloride according to general operatinginstructions 13.

158: ¹H-NMR (CDCl₃/D₆-DMSO): δ=0.80 ppm t (J=7.5 Hz, 3H); 1.65 m (2H);2.82 m (2H); 6.95 d (J=7.5 Hz, 1H); 7.08 dd (J=7.5, 2 Hz, 1H); 7.10-7.40m (10H); 7.61 d (J=2 Hz, 1H); 9.05 s (broad)(1H, NH).

159: ¹H-NMR (CDCl₃): δ=1.08 ppm t (J=7.5 Hz, 3H); 1.12 t (J=7.5 Hz, 3H);2.00 m (4H); 3.60 m (4H); 7.25-7.63 m (13H).

EXAMPLE 160N-(1,2-Diphenyl-1H-benzimidazol-5-yl)benzenemethanesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted withbenzenemethanesulfonic acid chloride according to general operatinginstructions 13.

Flash point 185-188° C.

EXAMPLE 161 6-[[1,2-Diphenyl-1H-benzimidazol-5-yl]amino]hexanoic acidmethyl ester EXAMPLE 1626-[N-(1,2-diphenyl-1H-benzimidazol-5-yl)-N-[(5-methoxycarbonyl)-pentyl]amino]hexanoicacid methyl ester

207 mg of 6-bromohexanoic acid methyl ester, 138 mg of potassiumcarbonate and 150 mg of sodium iodide were added to a solution of 285 mgof 5-amino-1,2-diphenyl-1H-benzimidazole in 5 ml of methanol, and it wasallowed to stir for 3 days at 20° C. It was mixed with water, extractedthree times with ethyl acetate, the combined organic phases were driedon sodium sulfate and concentrated by evaporation in a vacuum. Theresidue was chromatographed on silica gel.

161: Flash point 109-113° C.

162: ¹H-NMR (CDCl₃): δ=1.30-1.43 m (4H); 1.53-1.73 m (8H); 2.32 t (J=7.5Hz, 4H); 3.30 t (J=7.5 Hz, 4H); 3.68 s (6H); 6.75 dd (J=10, 2 Hz, 1H);7.10 d (J=10 Hz, 1H); 7.14 d (J=2 Hz, 1H); 7.23-7.35 m (5H); 7.42-7.58 m(5H).

EXAMPLE 163 6-[[1,2-Diphenyl-1H-benzimidazol-5-yl]amino]hexanoic acid

was obtained by reaction of6-[[1,2-diphenyl-1H-benzimidazol-5-yl]amino]hexanoic acid methyl esteraccording to general operating instructions 9.

¹H-NMR (D₆-DMSO): δ=1.35-1.50 ppm m (2H); 1.50-1.68 m (4H); 2.23 t(J=7.5 Hz, 2H); 3.05 t (J=7.5 Hz, 2H); 6.67 dd (J=10, 2 Hz, 1H); 6.80 d(J=2 Hz, 1H); 6.92 d (J=10 Hz, 1H); 7.30-7.40 m (4H); 7.45-7.62 m (6H).

EXAMPLE 1646-[[2-Phenyl-1-[4-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a)(5-Hydroxy-2-nitrophenyl)[(4-(phenylmethoxy)phenyl]amine

1 g of 3-fluoro-4-nitrophenol and 3.8 g of 4-benzyloxyaniline werestirred for 6.5 hours at 150° C. The batch was then diluted withdichloromethane. After two cycles of extraction with 1N aqueoushydrochloric acid and washing with water, it was extracted twice with 2Naqueous sodium hydroxide solution. The basic water phase was mixed withethyl acetate and 1N aqueous hydrochloric acid. After phase separation,the organic phase was extracted several times with 1N aqueoushydrochloric acid. After the organic phase was washed with saturatedsodium chloride solution, it was dried on sodium sulfate, concentratedby evaporation in a vacuum, and the residue was chromatographed onsilica gel.

¹H-NMR (D₆-DMSO): δ=5.14 ppm s (2H); 6.23 m (2H); 7.10 d (J=8 Hz, 2H);7.26 d (J=8 Hz, 2H); 7.32-7.52 m (5H); 8.03 d (J=8 Hz, 1H); 9.52 s (1H);10.71 s (1H).

b) 6-[[4-Nitro-3-[[4-(phenylmethoxy)phenyl]amino]-phenyl]oxy]hexanoicacid methyl ester

was obtained by reaction of(5-hydroxy-2-nitrophenyl)[(4-(phenylmethoxy)phenyl]amine with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.37-1.50 m (2H); 1.59-1.80 m (4H); 2.33 t (J=7.5 Hz,2H); 3.67 s (3H); 3.83 t (J=7.5 Hz, 2H); 5.12 s (2H); 6.24-6.33 m(2H);-7.04 d (J=8 Hz, 2H); 7.21 d (J=8 Hz, 2H); 7.32-7.50 m (5H); 8.17 d(J=8 Hz, 1H); 9.66 s (1H).

6-[[2-Phenyl-1-[4-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reduction of6-[[4-nitro-3-[[4-(phenylmethoxy)phenyl]amino]phenyl]oxy]hexanoic acidmethyl ester according to general operating instructions 2 andsubsequent cyclization with trimethyl orthobenzoate according to generaloperating instructions 3.

¹H-NMR (CDCl₃): δ=1.43-1.58 m (2H); 1.65-1.86 m (4H), 2.35 t (J=7.5 Hz,2H); 3.67 s (3H); 3.94 t (J=7.5 Hz, 2H); 5.14 s (2H); 6.64 d (J=2 Hz,1H); 6.95 dd (J=8, 2 Hz, 1H); 7.11 d (J=8 Hz, 2H); 7.18-7.61 m (12H);7.74 d (J=8 Hz, 1H).

EXAMPLE 1656-[[2-Phenyl-1-[4-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid

6-[[2-Phenyl-1-[4-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester was reacted according to general operatinginstructions 9.

¹H-NMR (D₆-DMSO): δ=1.36-1.62 m (4H); 1.65-1.78 m (2H); 2.22 t (J=7.5Hz, 2H); 3.92 t (J=7.5 Hz, 2H); 5.18 s (2H); 6.59 d (J=2 Hz, 1H); 6.92dd (J=8, 2 Hz, 1H); 7.20 d (J=8 Hz, 2H); 7.30-7.54 m (12H); 7.66 d (J=8Hz, 1H).

EXAMPLE 1666-[[1-(4-Hydroxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

6-[[2-Phenyl-1-[4-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid was reacted according to general operating instructions 1.

¹H-NMR (D₆-DMSO): δ=1.37-1.79 m (6H); 2.22 t (J=7.5 Hz, 2H); 3.92 t(J=7.5 Hz, 2H); 6.60 d (J=2 Hz, 1H); 6.91 dd (J=8, 2 Hz, 1H); 6.94 d(J=8 Hz, 2H); 7.20 d (J=8 Hz, 2H); 7.36 m (3H); 7.52 m (2H); 7.63 d (J=8Hz, 1H).

EXAMPLE 1676-[[2-Phenyl-1-[3-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a)(5-Hydroxy-2-nitrophenyl)[(3-(phenylmethoxy)phenyl]amine

1 g of 3-fluoro-4-nitrophenol and 3.81 g of 3-benzyloxyaniline werestirred for 22 hours at 150° C. Then, it was taken up in a littledichloromethane and chromatographed directly on silica gel.

¹H-NMR (CDCl₃): δ=5.10 ppm s (2H); 5.82 s (br) (1H); 6.27 dd (J=8, 2 Hz,1H); 6.48 d (J=2 Hz, 1H); 6.86 m (3H); 7.28-7.48 m (5H); 8.15 d (J=8 Hz,1H); 9.52 s (br) (1H); 10.71 s (1H).

b) 6-[[4-Nitro-3-[[3-(phenylmethoxy)phenyl]amino]phenyl]-oxy]hexanoicacid methyl ester

was obtained by reaction of(5-hydroxy-2-nitrophenyl)[(3-(phenylmethoxy)phenyl]amine with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=1.40-1.53 m (2H); 1.61-1.82 m (4H); 2.34 t (J=7.5 Hz,2H); 3.67 s (3H); 3.88 t (J=7.5 Hz, 2H); 5.10 s (2H); 6.33 dd (J=8, 2Hz, 1H); 6.58 d (J=2 Hz, 1H); 6.83-6.96 m (3H); 7.28-7.49 m (5H); 8.17 d(J=8 Hz, 1H); 9.74 s (br).

6-[[2-Phenyl-1-[3-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reduction of6-[[4-nitro-3-[[3-(phenylmethoxy)phenyl]amino]phenyl]oxy]hexanoic acidmethyl ester according to general operating instructions 2 andsubsequent cyclization with trimethyl orthobenzoate according to generaloperating instructions 3.

¹H-NMR (CDCl₃): δ=1.45-1.60 m (2H); 1.66-1.88 m (4H); 2.35 t (J=7.5 Hz,2H); 3.68 s (3H); 3.93 t (J=7.5 Hz, 2H); 5.02 s (2H); 6.69 d (J=2 Hz,1H); 6.90 m (2H); 6.97 dd (J=8, 2 Hz, 1H); 7.11 ddd (J=8, 2, 2 Hz, 1H);7.28-7.46 m (9H); 7.78 d (J=8 Hz, 1H).

EXAMPLE 168 ZK 212262 NEU+6-[[2-Phenyl-1-[3-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid

6-[[2-Phenyl-1-[3-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester was reacted according to general operatinginstructions 9.

¹H-NMR (CDCl₃): δ=1.49-1.62 m (2H), 1.67-1.88 m (4H); 2.39 t (J=7.5 Hz,2H); 3.93 t (J=7.5 Hz, 2H); 5.03 s (2H); 6.68 d (J=2 Hz, 1H); 6.91 m(3H), 6.98 dd (J=8, 2 Hz, 1H); 7.12 ddd (J=8, 2, 2 Hz, 1H); 7.29-7.47 m(8H); 7.57 d (J=8 Hz, 2H); 7.81 d (J=8 Hz, 1H).

EXAMPLE 1696-[[1-(3-Hydroxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

6-[[2-Phenyl-1-[3-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid was reacted according to general operating instructions 1.

¹H-NMR (D₆-DMSO): δ=1.39-1.80 m (6H); 2.23 t (J=7.5 Hz, 2H); 3.94 t(J=7.5 Hz, 2H); 6.57 d (J=2 Hz, 1H); 6.74 dd (J=2, 2 Hz, 1H); 6.84 dd(J=8, 2 Hz, 1H); 6.94 m (2H); 7.38 m (4H); 7.53 m (2H); 7.66 d (J=8 Hz,1H).

EXAMPLE 1706-[[1-(3-Hydroxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

6-[[2-Phenyl-1-[3-(phenylmethoxy)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester was reacted according to general operatinginstructions 1.

¹H-NMR (D₆-DMSO): δ=1.38-1.80 m (6H); 2.32 t (J=7.5 Hz, 2H); 3.59 s(3H); 3.94 t (J=7.5 Hz, 2H); 6.66 d (J=2 Hz, 1H); 6.74 dd (J=2, 2 Hz,1H); 6.83 dd (J=8, 2 Hz, 1H); 6.93 dd (J=8, 2 Hz, 2H); 7.38 m (4H); 7.54m (2H); 7.67 d (J=8 Hz, 1H).

EXAMPLE 1716-[[1-(3-Nitrophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidethyl ester

was obtained by reaction of6-hydroxy-1-(3-nitrophenyl)-2-phenylbenzimidazole (DE 4330959) with6-bromohexanoic acid ethyl ester according to general operatinginstructions 8.

Flash point 104-106° C.

EXAMPLE 1726-[[4-Bromo-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester a) 4-Bromo-6-methoxy-2-phenyl-1H-benzimidazole

36.6 g of 4-amino-3-bromo-5-nitroanisole (J. Chem. Soc. 1966, 1769) wasintroduced into 750 ml of ethanol and mixed with 19.8 g of iron powderand 126 ml of acetic acid. After being stirred for 2.5 hours at 55° C.,it was mixed with 350 ml of dichloromethane and made basic with 2Nsodium hydroxide solution. After filtration on Celite, it was washedwith water and saturated common salt solution and concentrated byevaporation. The crude phenyldiamine that was thus obtained was reactedwith trimethyl orthobenzoate according to general operating instructions3.

Flash point 203-205° C.

b) 4-Bromo-6-methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole

2.5 g of 4-bromo-6-methoxy-2-phenyl-1H-benzimidazole and 2.24 g of4-(methylbenzene)boronic acid were stirred with 1.5 g of anhydrouscopper(II) acetate and about 3 g of molecular sieve in 35 ml of pyridinefor 7 hours at 100° C. After dichloromethane and Celite were added, itwas concentrated by evaporation and chromatographed on silica gel with ahexane/ethyl acetate mixture.

Flash point 209-210° C.

c) 4-Bromo-6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole

1.2 g of 4-bromo-6-methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole,6 ml of acetic acid and 6 ml of aqueous hydrobromic acid (62%) areboiled for 5.5 hours. Then, it is precipitated with water, and theprecipitate is suctioned off. The latter was then dispersed betweenethyl acetate and 2N sodium hydroxide solution. After the organic phasewas washed with water, it was concentrated by evaporation.

Flash point 136-137° C.

6-[[4-Bromo-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of4-bromo-6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole with6-bromohexanoic acid methyl ester according to general operatinginstructions 8.

Flash point 136° C.

EXAMPLE 1736-[[4-Acetyl-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

0.5 g of 4-bromo-6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole,0.37 ml (α-ethoxyvinyl)tributyltin, and 140 mg ofdichlorobis(triphenylphosphine)palladium were stirred in 10 ml oftoluene for 18 hours at 100° C. After cooling, it was stirred with 2Naqueous hydrochloric acid for 0.25 hour. After phase separation, theorganic phase was washed with water and concentrated by evaporation. Theresidue was chromatographed on silica gel with a hexane/ethyl acetatemixture.

Flash point 114-115° C.

EXAMPLE 1746-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoic acidmethyl ster a) 5-Methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole

16.8 g of 5-methoxy-2-phenyl-1H-benzimidazole (Bull. Sci. Fac. Chim.Ind. Bologna, 11, 1953, 42) and 20.4 g of 4-(methylbenzene)boronic acidare reacted according to general operating instructions 14.

¹H-NMR (CDCl₃): δ=2.45 s (3H); 3.91 s (3H); 6.90 dd (J=8, 2 Hz, 1H);7.12 d (J=8 Hz, 1H); 7.18 d (J=8 Hz, 2H); 7.25-7.38 m (6H); 7.57 m (2H).

In addition, 6-methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole wasobtained.

b) 5-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole

was obtained from 5-methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazoleaccording to general operating instructions 6.

Flash point 270° C.

6-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoic acidmethyl ester

was obtained from 5-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazoleby reaction with 6-bromohexanoic acid methyl ester according to generaloperating instructions 8.

¹H-NMR (CDCl₃): δ=1.48-1.92 m (6H); 2.38 t (J=7.5 Hz, 2H); 2.46 s (3H);3.69 s (3H); 4.06 t (J=7.5 Hz, 2H); 6.89 dd (J=8, 2 Hz, 1H); 7.11 d (J=8Hz, 1H); 7.18 d (J=8 Hz, 2H); 7.24-7.37 m (6H), 7.57 m (2H).

EXAMPLE 1756-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoic acid

was obtained from6-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

¹H-NMR (D₆-DMSO) δ=1.41-1.67 m (4H); 1.70-1.83 m (2H); 2.26 t (J=7.5 Hz,2H); 2.43 s (3H); 4.05 t (J=7.5 Hz, 2H); 6.90 dd (J=8, 2 Hz, 1H); 7.04 d(J=8 Hz, 1H); 7.23-7.40 m (8H); 7.52 m (2H); 11.92 s (br.) (1H).

EXAMPLE 1766-[[2-Phenyl-1-[4-(thiomethyl)phenyl]-1H-benzimidazol-5-yl]oxy]hexanoicacid methyl ester a) 6-[[2-Phenyl]-1H-benzimidazol-5-yl]oxy]hexanoicacid methyl ester

4.84 g of 2-phenyl-5-hydroxy-1H-benzimidazole (Izv. Akad. Nauk. SSSRSer. Chim. 8, 1990, 1888) was obtained by reaction with 6-bromohexanoicacid methyl ester according to general operating instructions 8.

¹H-NMR (CDCl₃): δ=1.43-1.58 m (2H); 1.64-1.87 m (4H); 2.37 t (J=7.5 Hz,2H); 3.69 s (3H); 3.94 t (J=7.5 Hz, 2H); 6.87 dd (J=8, 2 Hz, 1H); 7.02 s(br.); 7.40-7.57 m (4H); 8.05 m (2H).

6-[[2-Phenyl-1-[4-(thiomethyl)phenyl]-1H-benzimidazol-5-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[2-phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic acid methyl ester with4-(thiomethylbenzene)boronic acid according to general operatinginstructions 14.

¹H-NMR (CDCl₃): δ=1.48-1.61 m (2H); 1.66-1.92 m (4H); 2.36 t (J=7.5 Hz,2H); 2.54 s (3H); 3.68 s (3H); 4.05 t (J=7.5 Hz, 2H); 6.90 dd (J=8, 2Hz, 1H); 7.11 d (J=8 Hz, 1H); 7.22 d (J=8 Hz, 2H); 7.27-7.49 m (6H);7.57 m (2H).

EXAMPLE 1776-[[2-Phenyl-1-[(4-thiomethyl)phenyl]-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[2-phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic acid methyl ester with4-(thiomethylbenzene)boronic acid according to general operatinginstructions 14.

¹H-NMR (CDCl₃): δ=1.45-1.57 m (2H); 1.62-1.86 m (4H); 2.44 t (J=7.5 Hz,2H); 2.56 s (3H); 3.66 s (3H); 3.93 t (J=7.5 Hz, 2H); 6.66 d (J=2 Hz,1H); 6.96 dd (J=8, 2 Hz, 1H); 7;18-7.39 m (7H); 7.54 m (2H); 7.73 d (J=8Hz, 1H).

EXAMPLE 178 6-[[2-Phenyl-1-(3-thienyl)-1H-benzimidazol-5-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[2-phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic acid methyl ester withthiophene-3-boronic acid according to general operating instructions 14.

¹H-NMR (CDCl₃): δ=1.48-1.62 m (2H); 1.66-1.92 m (4H); 2.47 t (J=7.5 Hz,2H); 3.68 s (3H); 4.04 t (J=7.5 Hz, 2H); 6.93 dd (J=8, 2 Hz, 1H); 6.98dd (J=5, 1 Hz, 1H); 7.18 d (J=8 Hz, 1H); 7.28 dd (J=3, 1 Hz, 1H);7.30-7.40 m (4H), 7.46 dd (J=5, 3 Hz, 1H); 7.60 m (2H).

EXAMPLE 179 6-[[2-Phenyl-1-(3-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[2-phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic acid methyl ester withthiophene-3-boronic acid according to general operating instructions 14.

¹H-NMR (CDCl₃): δ=1.45-1.58 m (2H); 1.64-1.87 m (4H); 2.35 t (J=7.5 Hz,2H); 3.67 s (3H); 3.97 t (J=7.5 Hz, 2H); 6.74 d (J=2 Hz, 1H); 6.95 dd(J=8, 2 Hz, 1H); 7.01 dd (J=5, 1 Hz, 1H); 7.29 dd (J=3, 1 Hz, 1H);7.30-7.38 m (4H); 7.47 dd (J=5, 3 Hz, 1H); 7.58 m (2H); 7.73 d (J=8 Hz,1H).

EXAMPLE 1804-[3-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenoxy]butanoicacid methyl ester a)6-(3-Methoxyphenoxy)-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole

was obtained from 6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazoleand 3-methoxybenzeneboronic acid according to general operatinginstructions 14.

Flash point 120-122° C.

b) 3-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenol

was obtained by reaction of6-(3-methoxyphenoxy)-1-(4-methylphenyl)-2-phenyl-1H-benzimidazoleaccording to general operating instructions 6 with the addition of 10mol % of hexadecyltributyl phosphonium bromide.

Flash point 252-253° C.

4-[3-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenoxy]butanoicacid methyl ester

was obtained by reaction of3-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenol with4-bromobutyric acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=2.00-2.13 nm (2H); 2.43 s (3H); 2.50 t (J=7.5 Hz, 2H);3.67 s (3H); 3.93 t (J=7.5 Hz, 2H); 6.44-6.62 m (3H); 6.95 d (J=2 Hz,1H); 7.06 dd (J=8, 2 Hz, 1H); 7.12-7.22 m (3H); 7.25-7.39 m (5H); 7.59 m(2H); 7.87 d (J=8 Hz, 1H).

EXAMPLE 1814-[4-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenoxy]butanoicacid methyl ester a)6-(4-Methoxyphenoxy)-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole

was obtained from 6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazoleand 4-methoxybenzeneboronic acid according to general operatinginstructions 14.

¹H-NMR (CDCl₃): δ=2.44 s (3H); 3.79 s (3H); 6.82-6.98 m (5H); 7.01 dd(J=8, 2 Hz, 1H); 7.17 d (J=8 Hz, 2H); 7.25-7.41 m (5H); 7.57 m (2H);7.82 d (J=8 Hz, 1H).

b) 4-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenol

was obtained by reaction of6-(3-methoxyphenoxy)-1-(4-methylphenyl)-2-phenyl-1H-benzimidazoleaccording to general operating instructions 6 with the addition of 10mol % of hexadecyltributyl phosphonium bromide.

¹H-NMR (D₆-DMSO): δ=2.38 s (3H); 6.61 d (J=2 Hz, 1H); 6.74 d (J=8 Hz,2H); 6.86 d (J=8 Hz, 2H); 6.91-7.01 m (2H); 7.22-7.41 m (6H); 7.49 m(2H); 7.75 d (J=8 Hz, 1H); 9.32 s (1H).

4-[4-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenoxy]butanoicacid methyl ester

was obtained by reaction of4-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenol with4-bromobutyric acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=2.03-2.16 m (2H); 2.42 s (3H); 2.53 t (J=7.5 Hz, 2H);3.69 s (3H); 3.97 t (J=7.5 Hz, 2H); 6.78-6.94 m (5H); 6.99 dd (J=8, 2Hz, 1H); 7.16 d (J=8, Hz, 2H); 7.24-7.38 m (5H); 7.57 m (2H); 7.79 d(J=8 Hz, 1H).

EXAMPLE 182[4-[[1-(4-Methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenoxy]aceticacid methyl ester

was obtained by reaction of4-[[1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]phenol withbromoacetic acid methyl ester according to general operatinginstructions 8.

¹H-NMR (CDCl₃): δ=2.43 s (3H); 3.82 s (3H); 4.61 s (2H); 6.78-6.96 m(5H); 7.00 dd (J=8, 2 Hz, 1H); 7.14 d (J=8, Hz, 2H); 7.23-7.38 m (5H);7.56 m (2H); 7.80 d (J=8 Hz, 1H).

EXAMPLE 183 4-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]butanoic acidmethyl ester

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with4-bromobutanoic acid methyl ester according to general operatinginstructions 8.

Flash point 107-110° C.

EXAMPLE 184 6-[[2-Phenyl-1-(3-pyridyl)-1H-benzimidazol-5-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[2-phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic acid methyl ester withpyridine-3-boronic acid according to general operating instructions 14.

MS (EI): 415 (molecular ion peak)

EXAMPLE 185 6-[[2-Phenyl-1-(3-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[2-phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic acid methyl ester withpyridine-3-boronic acid according to general operating instructions 14.

MS (EI): 415 (molecular ion peak)

EXAMPLE 186 6-[[2-Phenyl-1-(2-pyridyl)-1H-benzimidazol-5-yl]oxy]hexanoicacid

was obtained by reaction of6-[[2-phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic acid methyl ester with2-fluoro-pyridine according to general operating instructions 15.

MS (EI): 401 (molecular ion peak)

EXAMPLE 187 6-[[2-Phenyl-1-(2-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid

was obtained by reaction of6-[[2-phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic acid methyl ester with2-fluoro-pyridine according to general operating instructions 15.

MS (EI): 401 (molecular ion peak)

EXAMPLE 188 6-[[2-Phenyl-1-(4-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[2-phenyl]-1H-benzimidazol-5-yl]oxy]hexanoic acid methyl ester withpyridine-4-boronic acid according to general operating instructions 14.

MS (EI): 415 (molecular ion peak)

EXAMPLE 1896-[[2-(4-Fluorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-[[4-amino-3-(phenylamino)phenyl]oxy]hexanoic acid methyl ester with4-fluorobenzoyl chloride according to general operating instructions 5.

MS (EI): 432 (molecular ion peak)

EXAMPLE 1906-[[2-(4-Methoxyphenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-[[4-amino-3-(phenylamino)phenyl]oxy]hexanoic acid methyl ester with4-methoxybenzoyl chloride according to general operating instructions 5.

MS (EI): 444 (molecular ion peak)

EXAMPLE 1916-[[2-(3-Fluorophenyl)-1-phenyl-3H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-[[4-amino-3-(phenylamino)phenyl]oxy]hexanoic acid methyl ester with3-fluorobenzoyl chloride according to general operating instructions 5.

MS (EI): 432 (molecular ion peak)

EXAMPLE 1926-[[2-(4-Bromophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-[[4-amino-3-(phenylamino)phenyl]oxy]hexanoic acid methyl ester with4-bromobenzoyl chloride according to general operating instructions 5.

MS (EI): 492/494 (molecular ion peaks)

EXAMPLE 1936-[[2-[4-(Trifluoromethyl)phenyl]-1-phenyl-3-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-(phenylamino)phenyl]oxy]hexanoic acid methyl ester with4-(trifluoromethyl)benzoyl chloride according to general operatinginstructions 5.

MS (EI): 482 (molecular ion peak)

EXAMPLE 1946-[[2-(4-Fluorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was obtained by reaction of6-[2-(4-fluorophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester according to general operating instructions 9.

MS (EI): 418 (molecular ion peak).

EXAMPLE 1956-[[1-Phenyl-2-(benzothien-2-yl)-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction of6-[[4-amino-3-(phenylamino)phenyl]oxy]hexanoic acid methyl ester withbenzothiophene-2-carboxylic acid chloride according to general operatinginstructions 5.

Flash point 129-130° C.

EXAMPLE 1966-[[1-Phenyl-2-(benzothien-2-yl)-1H-benzimidazol-6-yl]oxy]hexanoic acid

was produced according to general operating instructions 9.

Flash point 340° C. (decomposition)

EXAMPLE 1976-[[5-Hydroxy-1-(4-methylphenyl)-2-phenyl-3H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester EXAMPLE 1986-[[6-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoicacid isopropyl ester

4,5-Dimethoxy-1,2-dinitrobenzene was hydrogenated to the diaminocompound according to general operating instructions 1, and saidcompound was cyclized with trimethyl orthobenzoate to5,6-dimethoxy-2-phenyl-1H-benzimidazole (flash point 131-133° C.) ascrude product according to general operating instructions 3. Thisbenzimidazole derivative was reacted with 4-methylphenylboronic acid to5,6-dimethoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole (flash point145-148° C.) according to general operating instructions 14. After ethercleavage with hydrobromic acid according to general operatinginstructions 6 to5,6-dihydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole (¹H-NMR ofhydrobromide (D₆-DMSO): δ=2.42 ppm s (3H); 6.68 s (1H); 7.22 s (1H);7.40-7.62 m (10H)), it was alkylated with 6-bromohexanoic acid isopropylester according to general operating instructions 8.6-[[5-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

flash point 137-139° C.

and6-[[6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoicacid isopropyl ester

flash point 177-178° C.

were obtained.

EXAMPLE 1996-[[5-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was produced according to general operating instructions 9.

Flash point 245-248° C.

EXAMPLE 2006-[[6-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoicacid

was produced according to general operating instructions 9.

Flash point 182-184° C.

EXAMPLE 2016-[[5-Methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester

6-[[5-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid isopropyl ester was methylated with methyl iodide according togeneral operating instructions 8.

Flash point 89-91° C.

EXAMPLE 2026-[[5-Methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was produced according to general operating instructions 9.

Flash point 184-186° C.

EXAMPLE 2036-[[5-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester and EXAMPLE 2046-[[6-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]-hexanoicacid methyl ester

were produced with 6-bromohexanoic acid methyl ester analogously to theisopropyl esters by alkylation of5,6-dihydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazole according togeneral operating instructions 8.6-[[5-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester was obtained.

¹H-NMR (CDCl₃): δ=1.45-1.58 ppm m (2H); 1.65-1.90 m (4H); 2.37 t (J=7.5Hz, 2H); 2.48 s (3H); 3.68 s (3H); 3.98 t (J=7.5 Hz, 2H); 5.68 s (broad)(1H, OH); 6.62 s (1H); 7.18 d (J=8 Hz, 2H); 7.22-7.38 m (5H); 7.40 s(1H); 7.53 dd (J=8, 1 Hz, 2H) and6-[[6-hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoicacid methyl ester.

Flash point 141-143° C.

EXAMPLE 2056-[[5-Methoxy-1-(4-methylphenyl)-2-phenyl-3H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

40 mg of6-[[5-methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid was dissolved in 2 ml of methanol, mixed with 1 drop ofconcentrated sulfuric acid, and the mixture was stirred for 2 hours. Itwas mixed with saturated potassium bicarbonate solution, diluted withwater, extracted with ethyl acetate, the extracts were dried on sodiumsulfate and concentrated by evaporation in a vacuum. The residue wascrystallized from diisopropyl ether.

Flash point 81-82° C.

EXAMPLE 2066-[[6-Methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]-hexanoicacid methyl ester

6-[[6-Hydroxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoicacid methyl ester was methylated with methyl iodide according to generaloperating instructions 8.

Flash point 108-110° C.

EXAMPLE 2076-[[6-Methoxy-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-5-yl]oxy]hexanoicacid

was produced according to general operating instructions 9.

Flash point 182-184° C.

EXAMPLE 2086-[(5-Amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]-hexanoicacid methyl ester a) 3-[(3,4-Dimethylphenyl)amino]-4,6-dinitrophenol

6.6 g of 3,4-dimethylaniline was added to a suspension that consists of4 g of 4,6-dinitro-3-fluorophenol (J. Org. Chem. 1991, 5958) in 100 mlof ethanol, and it was stirred for 7 days at 40° C. After cooling, itwas suctioned off, and the residue was recrystallized from ethanol.

¹H-NMR (CDCl₃): δ=2.20 ppm s (6H); 6.43 s (1H); 6.90-7.0 m (2H); 7.14 d(J=8 Hz, 1H); 9.08 s (1H), 9.70 s (broad) (1H); 10.2-10.6 (1H)

b) 6-[[3-[(3,4-Dimethylphenyl)amino]-4,6-dinitrophenyl]oxy]hexanoic acidmethyl ester

5 g of 3-[(3,4-dimethylphenyl)amino]-4,6-dinitrophenol was O-alkylatedwith 6-bromohexanoic acid methyl ester at 70° C. analogously to generaloperating instructions 8.

¹H-NMR (CDCl₃): δ=1.45-1.88 ppm m (6H); 2.30 s (6H); 2.33 t (J=7.5 Hz,2H); 3.68 s (3H); 3.88 t (J=7.5 Hz, 2H); 6.45 s (1H); 7.00-7.08 m (2H);7.25 d (J=8 Hz, 1H); 9.03 s (1H); 9.89 s (broad) (1H)

c)6-[(5-Amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester

2.45 g of6-[[3-[(3,4-dimethylphenyl)amino]-4,6-dinitrophenyl]oxy]hexanoic acidmethyl ester was hydrogenated in methanol according to general operatinginstructions 1. 500 mg of the crude product was reacted with benzimidatehydrochloride according to general operating instructions 4. Contrary togeneral operating instructions 4, after being taken up in solvent, thecrude product was not washed with aqueous hydrochloric acid.

¹H-NMR (CDCl₃): δ=1.48-1.58 ppm m (2H); 1.62-1.78 m (2H); 1.78-1.90 m(2H); 2.30 s (3H); 2.38 s (3H); 2.38 t (J=7.5 Hz, 2H); 3.67 s (3H); 3.93t (J=7.5 Hz, 2H); 6.56 s (1H); 6.98-7.08 m (2H); 7.18 s (1H); 7.20-7.32m (4H); 7.52 dd (J=8 Hz and 2 Hz, 2H)

EXAMPLE 2096-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

6-[(5-Amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester was reacted with 4-chlorobenzenesulfonic acid chlorideaccording to general operating instructions 13.

Flash point 186-191° C.

EXAMPLE 2106-[(5-Amino-2-(4-fluorophenyl)-1-(4-methoxyphenyl)-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester

was produced analogously to6-[(5-amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]-hexanoicacid methyl ester.

MS (EI): 4.77 (molecular ion peak)

EXAMPLE 2116-[(5-Amino-1-(4-methoxyphenyl)-2-(4-methoxyphenyl)-1H-benzimidazol-6-yl)oxy]-hexanoicacid methyl ester

was produced analogously to6-[(5-amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]-hexanoicacid methyl ester.

MS (EI): 489 (molecular ion peak)

EXAMPLE 2126-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-2-(4-fluorophenyl)-1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

6-[(5-Amino-2-(4-fluorophenyl)-1-(4-methoxyphenyl)-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester was reacted with 4-chlorobenzenesulfonic acid chlorideaccording to general operating instructions 13.

Flash point 180-182° C.

EXAMPLE 2136-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-(4-methoxyphenyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

6-[(5-Amino-1-(4-methoxyphenyl)-2-(4-methoxyphenyl)-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester was reacted with 4-chlorobenzenesulfonic acid chlorideaccording to general operating instructions 13.

Flash point 169-171° C.

EXAMPLE 2144-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]butanoicacid methyl ester

was produced analogously to6-[(5-amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]-hexanoicacid methyl ester.

¹H-NMR (CDCl₃): δ=2.17 ppm tt (J=8 and 8 Hz, 2H); 2.52 t (J=8 Hz, 2H);3.68 s (3H); 3.90 s (3H); 3.98 t (J=7.5 Hz, 2H); 6.54 s (1H); 7.0 d(J=12 Hz, 2H); 7.18-7.35 m (6H); 7.50-7.58 m (2H)

EXAMPLE 2154-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]butanoicacid methyl ester

4-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]butanoicacid methyl ester was reacted with 4-chlorobenzenesulfonic acid chlorideaccording to general operating instructions 13.

MS (EI): 605 (molecular ion peak)

EXAMPLE 2165-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]pentanoicacid methyl ester

was produced analogously to6-[(5-amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]-hexanoicacid methyl ester.

¹H-NMR (CDCl₃): δ=1.78-1.89 ppm m (4H); 2.32 t (J=8 Hz, 2H); 3.68 s(3H); 3.88 s (3H); 3.92 t (J=7.5 Hz, 2H); 6.53 s (1H); 7.0 d (J=12 Hz,2H); 7.18-7.36 m (6H); 7.48-7.58 m (2H)

EXAMPLE 2175-[[5-[[(4-Chlorophenyl)sulfonyl]-amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]pentanoicacid methyl ester

5-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]pentanoicacid methyl ester was reacted with 4-chlorobenzenesulfonic acid chlorideaccording to general operating instructions 13.

MS (EI): 619 (molecular ion peak)

EXAMPLE 2186-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester

was produced analogously to6-[(5-amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]-hexanoicacid methyl ester.

Flash point 129-131° C.

EXAMPLE 2196-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

6-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester was reacted with 4-chlorobenzenesulfonic acid chlorideaccording to general operating instructions 13.

Flash point 168-170° C.

EXAMPLE 2206-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was produced according to general operating instructions 9.

Flash point 181-182° C.

EXAMPLE 2216-[(5-Amino-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester

was produced analogously to6-[(5-amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]-hexanoicacid methyl ester.

Flash point 105-107° C.

EXAMPLE 2226-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

6-[(5-Amino-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester was reacted with 4-chlorobenzenesulfonic acid chlorideaccording to general operating instructions 13.

Flash point 189-191° C.

EXAMPLE 2236-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1-(4-methylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was produced according to general operating instructions 9.

Flash point 102-105° C.

EXAMPLE 224 5-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]pentanoicacid methyl ester

was produced analogously to6-[(5-amino-1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]-hexanoicacid methyl ester.

¹H-NMR (CDCl₃): δ=1.82-1.95 ppm m (4H); 2.39 t (J=8 Hz, 2H); 3.69 s(3H); 3.92-4.00 m (2H); 6.60 s (1H); 7.26-7.34 m (6H); 7.43-7.58 m (5H)

EXAMPLE 2255-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]pentanoicacid methyl ester

5-[(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl)oxy]pentanoic acid methylester was reacted with 4-chlorobenzenesulfonic acid chloride accordingto general operating instructions 13.

Flash point 157-161° C.

EXAMPLE 2265-[[5-[[(4-Chlorophenyl)sulfonyl]amino]-1,2-diphenyl-1H-benzimidazol-6-yl]oxy]pentanoicacid

was produced according to general operating instructions 9.

Flash point 236-242° C.

EXAMPLE 2276-[[5-[[(4-Fluorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

6-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester was reacted with 4-fluorobenzenesulfonic acid chlorideaccording to general operating instructions 13.

MS (EI): 617 (molecular ion peak)

EXAMPLE 2286-[[5-[[(4-(Trifluoromethyl)phenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

6-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester was reacted with 4-(trifluoromethyl)benzenesulfonicacid chloride according to general operating instructions 13.

MS (EI): 668 (molecular ion peak)

EXAMPLE 2296-[[5-[[(4-Trifluorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid

was produced according to general operating instructions 9.

Flash point 190-192° C.

EXAMPLE 2306-[[5-[[(4-chlorophenyl)sulfonyl]methylamino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

100 mg of6-[[5-[[(4-chlorophenyl)sulfonyl]amino]-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester was dissolved in 3 ml of tetrahydrofuran. 10 mg ofsodium hydride was added to it at 0° C., it was allowed to stir for 30minutes, then 50 μl of methyl iodide was added in drops, and it wasallowed to stir for another 60 minutes at 0° C. It was mixed withsaturated ammonium chloride solution, extracted three times with ethylacetate, the organic phases were washed with water, dried on sodiumsulfate and concentrated by evaporation in a vacuum. The residue waschromatographed on silica gel.

Flash point 178-180° C.

EXAMPLE 231[[(4-Chlorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]aceticacid methyl ester

100 mg of4-chloro-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamide wassuspended in 0.5 ml of N,N-dimethylformamide, mixed with 8 mg of sodiumhydride and stirred for 30 minutes at 20° C. 50 mg of bromoacetic acidmethyl ester was added, allowed to stir for 15 hours, mixed with water,extracted three times with ethyl acetate, the extracts were dried onsodium sulfate, concentrated by evaporation in a vacuum, and the residuewas chromatographed on silica gel.

¹H-NMR (CDCl₃): δ=3.70 ppm s (3H); 4.52 s (2H); 7.20 d (J=8 Hz, 1H);7.26-7.58 m (14H); 7.70 d (J=10 Hz, 2H)

EXAMPLE 232[[(4-Chlorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]aceticacid

was produced according to general operating instructions 9.

Flash point 248° C.

EXAMPLE 2334-[[(4-Chlorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]butanoicacid methyl ester

100 mg of4-chloro-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamide wassuspended in 0.5 ml of N,N-dimethylformamide, mixed with 6 mg of sodiumhydride and stirred for 30 minutes at 20° C. 56 mg of 4-bromobutyricacid methyl ester was added, it was allowed to stir for 15 hours, mixedwith water, extracted three times with ethyl acetate, the extracts weredried on sodium sulfate, concentrated by evaporation in a vacuum, andthe residue was digested with diisopropyl ether.

Flash point 54-58° C.

EXAMPLE 2344-[[(4-Chlorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]butanoicacid

was produced according to general operating instructions 9.

Flash point 249-254° C.

EXAMPLE 2355-[[(4-Chlorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]pentanoicacid methyl ester

100 mg of4-chloro-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamide wassuspended in 0.5 ml of N,N-dimethylformamide, mixed with 8 mg of sodiumhydride and stirred for 30 minutes at 20° C. 60 mg of 5-bromopentanoicacid methyl ester was added, it was allowed to stir for 15 hours, mixedwith water, extracted three times with ethyl acetate, the extracts weredried on sodium sulfate, concentrated by evaporation in a vacuum, andthe residue was chromatographed on silica gel.

¹H-NMR (CDCl₃): δ=1.46-1.54 ppm m (2H); 1.62-1.78 m (2H); 2.30 t (J=8Hz, 2H); 3.62 s (3H); 3.62 t (J=8 Hz, 2H); 7.12-7.53 m (17H)

EXAMPLE 2365-[[(4-Chlorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]pentanoicacid

was produced according to general operating instructions 9.

Flash point 123-127° C.

EXAMPLE 2376-[[(4-Chlorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]hexanoic-acidmethyl ester

6-[[1,2-Diphenyl-1H-benzimidazol-5-yl]amino]hexanoic acid methyl esterwas reacted with 4-chlorobenzenesulfonic acid chloride according togeneral operating instructions 13.

MS (EI): 588 (molecular ion peak)

EXAMPLE 2387-[[(4-Chlorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]heptanoicacid methyl ester

100 mg of4-chloro-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamide wassuspended in 0.5 ml of N,N-dimethylformamide, mixed with 8 mg of sodiumhydride, and stirred for 30 minutes at 20° C. 70 mg of 7-bromoheptanoicacid methyl ester was added, it was allowed to stir for 15 hours, mixedwith water, extracted three times with ethyl acetate, the extracts weredried on sodium sulfate, concentrated by evaporation in a vacuum, andthe residue was chromatographed on silica gel.

¹H-NMR (CDCl₃): δ=1.26-1.64 ppm m (8H); 2.27 t (J=8 Hz, 2H); 3.60 t (J=8Hz, 2H); 3.68 s (3H); 7.12 dd (J=10, 2 Hz, 1H); 7.22 d (J=10 Hz, 1H);7.30-7.61 m (15H)

EXAMPLE 2397-[[(4-Chlorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]heptanoicacid

was produced according to general operating instructions 9.

Flash point 172-178° C.

EXAMPLE 240N-(1,2-Diphenyl-1H-benzimidazol-5-yl)-4-fluorobenzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with4-fluorobenzenesulfonic acid chloride according to general operatinginstructions 13.

Flash point 209-214° C.

EXAMPLE 2416-[[(4-Fluorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]hexanoicacid methyl ester

150 mg ofN-(1,2-diphenyl-1H-benzimidazol-5-yl)-4-fluorobenzenesulfonamide wassuspended in 0.5 ml of N,N-dimethylformamide, mixed with 12 mg of sodiumhydride and stirred for 30 minutes at 20° C. 98 mg of 6-bromohexanoicacid methyl ester was added, allowed to stir for 15 hours, mixed withwater, extracted three times with ethyl acetate, the extracts were driedon sodium sulfate, concentrated by evaporation in a vacuum, and theresidue was chromatographed on silica gel.

Flash point 128-134° C.

EXAMPLE 2426-[[(4-Fluorophenyl)sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]amino]hexanoicacid

was produced according to general operating instructions 9.

Flash point 200-210° C.

EXAMPLE 2436-[[[4-(Trifluoromethyl)phenyl]sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]-amino]hexanoicacid methyl ester

150 mg of4-(trifluoromethyl)-N-(1,2-diphenyl-1H-benzimidazol-5-yl)benzenesulfonamidewas suspended in 0.5 ml of N,N-dimethylformamide, mixed with 11 mg ofsodium hydride and stirred for 30 minutes at 20° C. 88 mg of6-bromohexanoic acid methyl ester was added, it was allowed to stir for15 hours, mixed with water, extracted three times with ethyl acetate,the extracts were dried on sodium sulfate, concentrated by evaporationin a vacuum, and the residue was digested with diisopropyl ether.

Flash point 359-161° C.

EXAMPLE 2446-[[[4-(Trifluoromethyl)phenyl]sulfonyl][1,2-diphenyl-1H-benzimidazol-5-yl]-amino]hexanoicacid

was produced according to general operating instructions 9.

Flash point 224-230° C.

EXAMPLE 2454-Chloro-N-[1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-5-yl]benzenesulfonamidea) (2,4-Dinitrophenyl)(4-methoxyphenyl)amine

1.43 g of 4-(2,4-dinitroanilino)phenol, 500 mg of potassium carbonateand 0.32 ml of methyl iodide were stirred in 5 ml ofN,N-dimethylformamide for 2 days at 20° C. The mixture was poured ontowater, extracted three times with ethyl acetate, the extracts were driedon sodium sulfate, concentrated by evaporation in a vacuum, and theresidue was chromatographed on silica gel.

Flash point 117-127° C.

b) 5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazole

(2,4-Dinitrophenyl)(4-methoxyphenyl)amine was hydrogenated according togeneral operating instructions 1. The crude product was cyclized withtrimethyl orthobenzoate to the benzimidazole derivative according togeneral operating instructions 3.

¹H-NMR (CDCl₃): δ=3.88 ppm s (3H); 6.70 dd (J=12, 2 Hz, 1H); 6.95-7.06 m(4H); 7.18-7.38 m (7H); 7.53-7.65 m (2H)

c)4-Chloro-N-[1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-5-yl]benzenesulfonamide

5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazole was reacted with4-chlorobenzenesulfonic acid chloride according to general operatinginstructions 13.

Flash point 238-24° C.

EXAMPLE 2466-[[(4-Chlorophenyl)sulfonyl][1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-5-yl]amino]hexanoicacid methyl ester

75 mg of4-chloro-N-[1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-5-yl]benzenesulfonamidewas suspended in 0.5 ml of N,N-dimethylformamide, mixed with 6 mg ofsodium hydride and stirred for 30 minutes at 20° C. 44 mg of6-bromohexanoic acid methyl ester was added, allowed to stir for 15hours, mixed with water, extracted three times with ethyl acetate, theextracts were dried on sodium sulfate, concentrated by evaporation in avacuum, and the residue was chromatographed on silica gel.

MS (EI): 617 (molecular ion peak)

EXAMPLE 2476-[[(4-Chlorophenyl)sulfonyl][1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-5-yl]amino]hexanoicacid

was produced according to general operating instructions 9.

Flash point 205-208° C.

EXAMPLE 2482,2-Dimethyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

a) 2,2-Dimethyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanonitrilewas obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with6-bromo-1,1-dimethylhexanonitrile according to general operatinginstructions 8.

Flash point 115-118° C.

b) 2,2-Dimethyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

500 mg of2,2-dimethyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanonitrile wasrefluxed for 2 hours in 5 ml of 80% sulfuric acid. After cooling, it wascarefully added to ice water, the pH was set at 8 with sodium hydroxidesolution, it was extracted three times with ethyl acetate, the extractswere dried on sodium sulfate, and it was concentrated by evaporation ina vacuum. The residue was chromatographed on silica gel.

Flash point 115-118° C.

EXAMPLE 249 8-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]octanoic acidmethyl ester

was obtained by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with8-bromooctanoic acid methyl ester according to general operatinginstructions 8.

Flash point 92-95° C.

EXAMPLE 250 8-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]octanoic acid

was produced according to general operating instructions 9.

Flash point 136-140° C.

EXAMPLE 2516-[[1-(Indan-5-yl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was produced analogously to6-[[1-(3,4-dimethylphenyl-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester.

Flash point 81-85° C.

EXAMPLE 2526-[[1-(Indan-5-yl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was produced according to general operating instructions 9.

Flash point 176-180° C.

EXAMPLE 2537-[[1-(Indan-5-yl)-2-phenyl-1H-benzimidazol-6-yl]oxy]heptanoic acidmethyl ester

was produced analogously to6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester.

Flash point 92-98° C.

EXAMPLE 2547-[[1-(Indan-5-yl)-2-phenyl-1H-benzimidazol-6-yl]oxy]heptanoic acid

was produced according to general operating instructions 9.

Flash point 175-178° C.

EXAMPLE 2556-[[1-(3-Fluorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was produced-analogously to6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester.

Flash point 104-106° C.

EXAMPLE 2566-[[1-(3-Fluorophenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was produced according to general operating instructions 9.

Flash point 149-151° C.

EXAMPLE 2576-[[2-(4-Nitrophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester a) 6-Methoxy-2-(4-nitrophenyl)-1-phenyl-1H-benzimidazole

200 mg of 4-methoxy-N²-phenyl-o-phenylenediamine was dissolved in 5 mlof N,N-dimethylformamide, mixed with 346 mg of EEDQ and 234 mg of4-nitrobenzoic acid, and the mixture was stirred for 5 hours at 100° C.After cooling, it was mixed with water. The precipitate was suctionedoff and purified by column chromatography, taken up in 6N hydrochloricacid and refluxed for 2 hours. After cooling, it was added in drops tosaturated potassium bicarbonate solution. The precipitate was suctionedoff and dried.

Flash point 189-191° C.

b) 6-Hydroxy-2-(4-nitrophenyl)-1-phenyl-1H-benzimidazole

was obtained by reaction according to general operating instructions 6.

¹H-NMR (D₆-DMSO): δ=6.56 ppm d (J=2 Hz, 1H); 6.87 dd (J=10, 2 Hz, 1H);7.46 dd (J=10, 2 Hz, 2H); 7.53-7.70 m (4H); 7.75 d (J=10 Hz, 2H); 8.20 d(J=10 Hz, 2H); 9.55 s (broad) (1H)

c) 6-[[2-(4-Nitrophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was obtained by reaction according to general operating instructions 8.

¹H-NMR (CDCl₃): δ=1.45-1.55 ppm m (2H); 1.62-1.84 m (4H); 2.33 t (J=8Hz, 2H); 3.68 s (3H); 3.95 t (J=8 Hz, 2H); 6.67 d (J=2 Hz, 1H); 7.00 dd(J=10, 2 Hz, 1H); 7.28-7.38 m (2H); 7.52-7.60 m (3H); 7.71 d (J=10 Hz,2H); 7.77 d (J=10 Hz, 1H); 8.13 d (J=10 Hz, 2H)

EXAMPLE 2586-[[2-(4-Nitrophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanoic acid

was produced according to general operating instructions 9.

Flash point 181-186° C.

EXAMPLE 2596-[[1-Phenyl-2-(3-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester

was produced analogously to6-[[1-phenyl-2-(4-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acidmethyl ester.

Flash point 159-160° C.

EXAMPLE 260N-(Cyclopropylmethoxy)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 18.

MS (EI): 469 (molecular ion peak)

EXAMPLE 261N-Isobutoxy-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 18.

MS (EI): 471 (molecular ion peak)

EXAMPLE 262N-(Phenylmethoxy)-6-[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl)oxy]-hexanamide

A solution that consists of 50 mg of6-[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl)oxy]hexanoicacid in 1 ml of tetrahydrofuran was added to a solution that consists of17 mg of carbonyl diimidazole in 1 ml of tetrahydrofuran, it was stirredfor 30 minutes at 20° C. and refluxed for 30 minutes. At 20° C., 16 mgof O-benzylhydroxylamine hydrochloride was added, and it was allowed tostir for 20 hours. For working-up, ethyl acetate was added, extractedwith 2N hydrochloric acid and saturated sodium bicarbonate solution,dried on sodium sulfate and concentrated by evaporation in a vacuum. Theresidue was purified by column chromatography on silica gel.

Flash point 145-148° C.

EXAMPLE 263N-(Cyclopropylmethoxy)-6-[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl)oxy]hexanamide

was produced analogously toN-(phenylmethoxy)-6-[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl)oxy]hexanamide.

MS (EI): 559 (molecular ion peak)

EXAMPLE 264N-Isobutoxy-6-[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl)oxy]hexanamide

was produced analogously toN-(phenylmethoxy)-6-[2-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-6-yl)oxy]hexanamide.

¹H-NMR (CDCl₃): δ=0.94 ppm d (J=8 Hz, 6H); 1.48-2.03 m (7H); 2.05-2.18 m(2H); 3.60-3.72 m (2H); 3.76 s (6H); 3.90-4.00 m (2H); 3.96 s (3H); 6.50s (2H); 6.72 d (J=2 Hz, 1H); 6.95 dd (J=10, 2 Hz, 1H); 7.28-7.38 m (3H);7.55-7.62 m (2H); 7.74 d (J=10 Hz, 1H); 8.20 s (broad) (1H)

EXAMPLE 265N-Isopropyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 17.

Flash point 107-112° C.

EXAMPLE 266N,N-Dimethyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 17.

Flash point 83-88° C.

EXAMPLE 2676-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]-1-pyrrolidin-1-ylhexan-1-one

was produced according to general operating instructions 17.

Flash point 84-88° C.

EXAMPLE 268N-(2-Methoxyethyl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 17.

Flash point 63-68° C.

EXAMPLE 269N-(3-Methoxypropyl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 18.

Flash point 84-91° C.

EXAMPLE 270N-Isobutyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 17.

¹H-NMR (CDCl₃): δ=0.90 ppm d (J=8 Hz, 6H); 1.44-1.57 m (2H); 1.65-1.85 m(5H); 2.20 t (J=8 Hz, 2H); 3.08 t (J=8 Hz, 2H); 3.94 t (J=8 Hz, 2H);6.68 d (J=2 Hz, 1H); 6.96 dd (J=10, 2 Hz, 1H); 7.25-7.38 m (5H);7.45-7.58 m (5H); 7.75 d (J=10 Hz, 1H)

EXAMPLE 271N-[[2,2-Dimethylamino)ethyl]-N-methyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)-oxy]hexanamide

was produced according to general operating instructions 17.

¹H-NMR (CDCl₃) (signal of the main rotamer): δ=1.44-1.57 ppm m (2H);1.64-1.84 m (4H); 2.30 s (6H); 2.34 t (J=8 Hz, 2H); 2.47 t (J=8 Hz, 2H);3.00 s (3H); 3.50 t (J=8 Hz, 2H); 3.94 t (J=8 Hz, 2H); 6.69 d (J=2 Hz,1H); 6.96 dd (J=10, 2 Hz, 1H); 7.25-7.36 m (5H); 7.45-7.56 m (5H); 7.73d (J=10 Hz, 1H)

EXAMPLE 272N-(2-Methoxyethyl)-N-methyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 17.

¹H-NMR (CDCl₃) (signal of the main rotamer): δ=1.43-1.58 ppm m (2H);1.63-1.84 m (4H); 2.33 t (J=8 Hz, 2H); 3.07 s (3H); 3.32 s (3H);3.47-3.58 m (4H); 3.95 t (J=8 Hz, 2H); 6.70 d (J=2 Hz, 1H); 6.96 dd(J=10, 2 Hz, 1H); 7.25-7.35 m (5H); 7.45-7.55 m (5H); 7.75 d (J=10 Hz,1H)

EXAMPLE 2736-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]-1-morpholin-1-ylhexan-1-one

was produced according to general operating instructions 17.

¹H-NMR (CDCl₃): δ=1.47-1.59 ppm m (2H); 1.63-1.88 m (4H); 2.34 t (J=8Hz, 2H); 3.42-3.49 m (2H); 3.57-3.70 m (6H); 3.94 t (J=8 Hz, 2H); 6.68 d(J=2 Hz, 1H); 6.96 dd (J=10, 2 Hz, 1H); 7.23-7.38 m (5H); 7.45-7.56 m(5H); 7.75 d (J=10 Hz, 1H)

EXAMPLE 274N,N-Di(-2-methoxyethyl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 18.

Flash point 88-98° C.

EXAMPLE 275N-Isopentyl-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 18.

Flash point 127-129° C.

EXAMPLE 276N-(Pyridin-2-yl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 18.

Flash point 120-124° C.

EXAMPLE 277N-(Pyridin-3-yl)-6-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]hexanamide

was produced according to general operating instructions 18.

Flash point 154° C.

EXAMPLE 2786-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]-1-piperidin-1-ylhexan-1-one

was produced according to general operating instructions 18.

Flash point 93-98° C.

EXAMPLE 279[6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]-1-hexanoyl]piperidine-4-carbonamide

was produced according to general operating instructions 17.

Flash point 177-178° C.

EXAMPLE 280[[6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]-1-hexanoyl]methylamino]-aceticacid ethyl ester

was produced according to general operating instructions 17.

¹H-NMR (CDCl₃) (signal of the main rotamer): δ=1.23 ppm t (J=8 Hz, 3H);1.45-1.88 m (6H); 2.40 t (J=8 Hz, 2H); 3.08 s (3H); 3.93 t (J=8 Hz, 2H);4.12 s (2H); 4.18 q (J=8 Hz; 2H); 6.70 d (J=2 Hz, 1H); 6.97 dd (J=10, 2Hz, 1H) 7.23-7.35 m (5H); 7.45-7.58 m (5H); 7.75 d (J=10 Hz, 1H)

EXAMPLE 2814-[[6-[(1,2-Diphenyl-1H-benzimidazol-6-yl)oxy]-1-hexanoyl]]piperazine-1-carboxylicacid ethyl ester

was produced according to general operating instructions 17.

¹H-NMR (CDCl₃): δ=1.27 ppm t (J=8 Hz, 3H); 1.45-1.60 m (2H); 1.63-1.88 m(4H); 2.36 t (J=8 Hz, 2H); 3.40-3.53 m (6H); 3.56-3.64 m (2H); 3.93 t(J=8 Hz, 2H); 4.15 q (J=8 Hz, 2H); 6.69 d (J=2 Hz, 1H); 6.96 dd (J=10, 2Hz, 1H); 7.23-7.38 m (5H); 7.45-7.56 m (5H); 7.76 d (J=10 Hz, 1H)

EXAMPLE 282N-Isopropyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

MS (EI): 469 (molecular ion peak)

EXAMPLE 283N,N-Dimethyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]-hexanamide

was produced according to general operating instructions 18.

MS (EI): 455 (molecular ion peak)

EXAMPLE 284N,N-Diethyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

MS (EI): 483 (molecular ion peak)

EXAMPLE 285N-Isobutyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

¹H-NMR (CDCl₃): δ=0.90 ppm d (J=8 Hz, 6H); 1.44-1.55 m (2H); 1.58-1.83 m(5H); 2.20 t (J=8 Hz, 2H); 2.30 s (3H); 2.35 s (3H); 3.09 t (J=8 Hz,2H); 3.94 t (J=8 Hz, 2H); 6.63 d (J=2 Hz, 1H); 6.94 dd (J=10, 2 Hz, 1H);7.02 dd (J=10, 2 Hz, 1H); 7.10 d (J=2 Hz, 1H); 7.22-7.35 m (4H); 7.56 ddJ=8 Hz, and 2 Hz, 2H); 7.73 d (J=10 Hz, 1H)

EXAMPLE 286N-Cyclopropyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]-hexanamide

was produced according to general operating instructions 18.

MS (EI): 467 (molecular ion peak)

EXAMPLE 287N-Cyclobutyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]-oxy]hexanamide

was produced according to general operating instructions 18.

¹H-NMR (CDCl₃): δ=1.42-1.55 ppm m (2H); 1.60-1.88 m (8H); 2.15 t (J=8Hz, 2H); 2.28-2.40 m (2H); 2.30 s (3H); 2.35 s (3H); 3.93 t (J=8 Hz,2H); 4.40 quintet (J=8 Hz, 2H); 5.55 s (broad) (1H); 6.63 d (J=2 Hz,1H); 6.92 dd (J=10, 2 Hz, 1H); 7.03 dd (J=10 Hz, and 2 Hz; 1H); 7.08 d(J=2 Hz, 1H); 7.20-7.36 m (4H); 7.57 dd (J=8, 2 Hz, 2H); 7.72 d (J=10Hz, 1H)

EXAMPLE 288N-tert-Butyl-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

¹H-NMR (CDCl₃): δ=1.32 ppm s (9H); 1.42-1.55 m (2H); 1.62-1.82 m (4H);2.10 t (J=8 Hz, 2H); 2.30 s (3H); 2.36 s (3H); 3.92 t (J=8 Hz, 2H); 5.23s (broad) (1H); 6.66 d (J=2 Hz, 1H); 6.93 dd (J=10, 2 Hz, 1H); 7.02 dd(J=10 Hz, and 2 Hz, 1H); 7.02 s (broad) (1H); 7.22-7.36 m (4H); 7.56 dd(J=8, 2 Hz, 2H); 7.73 d (J=10 Hz, 1H)

EXAMPLE 289(R)-6-[[1-(3,4-Dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]1-(2-methoxy-methyl)pyrrolidin-1-ylhexan-1-one

was produced according to general operating instructions 18.

MS (EI): 467 (molecular ion peak)

EXAMPLE 290N-(3-Imidazol-1-yl-propyl)-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

¹H-NMR (CDCl₃): δ=1.42-1.53 ppm m (2H); 1.62-2.02 m (6H); 2.17 t (J=8Hz, 2H); 2.27 s (3H); 2.34 s (3H); 3.24 q (J=8 Hz, 2H); 3.92 t (J=8 Hz,2H); 3.96 t (J=8 Hz, 2H); 5.68 s (broad) (1H); 6.63 d (J=2 Hz, 1H);6.88-6.95 m (2H); 7.00 dd (J=10 Hz, and 2 Hz, 1H); 7.04-7.10 m (2H);7.20-7.36 m (4H); 7.50 s (broad) (1H); 7.53 dd (J=8, 2 Hz, 2H); 7.72 d(J=10 Hz, 1H)

EXAMPLE 291N-(2-Pyridin-2-ylethyl)-6-[[1-(3,4-dimethylphenyl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

¹H-NMR (CDCl₃): δ=1.38-1.52 ppm m (2H); 1.62-1.82 m (4H); 2.15 t (J=8Hz, 2H); 2.30 s (3H); 2.35 s (3H); 2.96 t (J=8 Hz, 2H); 3.66 q (J=8 Hz,2H); 3.90 t (J=8 Hz, 2H); 6.48 s (broad) (1H); 6.65 d (J=2 Hz, 1H); 6.92dd (J=10, 2 Hz, 1H); 7.00 d (J=10 Hz, and 2 Hz, 1H); 7.06-7.38 m (7H);7.53-7.62 m (3H); 7.72 d (J=10 Hz, 1H); 8.50 d (broad) (J=6 Hz, 1H)

EXAMPLE 292N,N-Dimethyl-6-[[2-(4-nitrophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

¹H-NMR (CDCl₃): δ=1.46-1.58 ppm m (2H); 1.64-1.88 m (4H); 2.32 t (J=8Hz, 2H); 2.93 s (3H); 3.00 s (3H); 3.96 t (J=8 Hz, 2H); 6.65 d (J=2 Hz,1H); 7.00 dd (J=10, 2 Hz, 1H); 7.28-7.36 m (2H); 7.53-7.61 m (3H); 7.70d (J=10 Hz, 2H); 7.76 d (J=8 Hz, 1H); 8.13 d (J=8 Hz, 2H)

EXAMPLE 293N-Isopropyl-6-[[2-(4-nitrophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

Flash point 162-165° C.

EXAMPLE 294N-Isopentyl-6-[[2-(4-nitrophenyl)-1-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

Flash point 148-154° C.

EXAMPLE 295N-(3-Methoxypropyl)-6-[[2-(4-nitrophenyl)-1-phenyl-1H-benzimidazol-6-yl]-oxy]hexanamide

was produced according to general operating instructions 18.

Flash point 104-110° C.

EXAMPLE 296N-(3-Methoxypropyl)-6-[[1-(indan-5-yl)-2-phenyl-1H-benzimidazol-6-yl]oxy]hexanamide

was produced according to general operating instructions 18.

¹H-NMR (CDCl₃): δ=1.43-1.56 ppm m (2H); 1.62-1.85 m (6H); 2.10-2.23 m(4H); 2.95 t (J=10 Hz, 2H); 3.00 t (J=10 Hz, 2H); 3.32 s (3H); 3.32-3.40m (2H); 3.48 t (J=8 Hz, 2H); 3.93 t (J=8 Hz, 2H); 6.03 s (broad) (1H);6.67 d (J=2 Hz, 1H); 6.93 dd (j=10, 2 Hz, 1H); 7.03 dd (J=10, 2 Hz, 1H);7.12 s (broad) (1H); 7.26-7.35 m (4H); 7.55 dd (J=10 Hz, 2H); 7.72 d(J=8 Hz, 1H)

EXAMPLE 2976-[[1-(4-Methylphenyl)-2-(3-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]-oxy]hexanoic acid methylester with 3-pyridylcarbaldehyde according to general operatinginstructions 16.

MS (EI): 429 (molecular ion peak)

EXAMPLE 2986-[[1-(4-Methylphenyl)-2-(4-pyridyl)-1H-benzimidazol-6-yl)oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]-oxy]hexanoic acid methylester with 4-pyridylcarbaldehyde according to general operatinginstructions 16;

MS (EI): 429 (molecular ion peak)

EXAMPLE 2996-[[1-(4-Methylphenyl)-2-(2-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]-oxy]hexanoic acid methylester with 2-thienylcarbaldehyde according to general operatinginstructions 16.

MS (EI): 434 (molecular ion peak)

EXAMPLE 3006-[[1-(4-Methylphenyl)-2-(3-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]oxy]hexanoic acid methylester with 3-thienylcarbaldehyde according to general operatinginstructions 16.

MS (EI): 434 (molecular ion peak)

EXAMPLE 3016-[[2-(3-Indolyl)-1-(4-methylphenyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]-oxy]hexanoic acid methylester with 3-indolylcarbaldehyde according to general operatinginstructions 16.

MS (EI): 467 (molecular ion peak)

EXAMPLE 3026-[[1-(4-Methylphenyl)-2-(2-furyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]-oxy]hexanoic acid methylester with 2-furylcarbaldehyde according to general operatinginstructions 16.

MS (EI): 418 (molecular ion peak)

EXAMPLE 3036-[[1-(4-Methylphenyl)-2-(3-furyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]-oxy]hexanoic acid methylester with 3-furylcarbaldehyde according to general operatinginstructions 16.

MS (EI): 418 (molecular ion peak)

EXAMPLE 3046-[[1-(4-Methylphenyl)-2-(5-methyl-2-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]-oxy]hexanoic acid methylester with 5-methyl-2-thienyl-carbaldehyde according to generaloperating instructions 16.

MS (EI): 448 (molecular ion peak)

EXAMPLE 3056-[[1-(4-Methylphenyl)-2-(4-bromo-2-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]-oxy]hexanoic acid methylester with 4-bromo-2-thienylcarbaldehyde according to general operatinginstructions 16.

MS (EI): 512/514 (molecular ion peak)

EXAMPLE 3066-[[1-(4-Methylphenyl)-2-(3-methyl-2-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoicacid methyl ester

was obtained by reaction of6-[[4-amino-3-((4-methylphenyl)amino)phenyl]-oxy]hexanoic acid methylester with 3-methyl-2-thienylcarbaldehyde according to general operatinginstructions 16.

MS (EI): 448 (molecular ion peak)

EXAMPLE 307 Inhibition of Microglia Activation

For in vitro production of Aβ-activated microglia, primary rat microgliawith synthetic Aβ-peptide are incubated:

For simulation of Aβ deposits, synthetic Aβ peptide is dried on 96-holetissue culture plates. A peptide stock solution is diluted by 2 mg/ml ofH₂O 1:50 in H₂O. To coat the 96-hole plates, 30 μl of this dilutepeptide solution/hole is used, and it is dried overnight at roomtemperature.

Primary rat microglia are harvested by mixed glia cultures, which wereobtained from P3 rat brains. In the production of mixed glia cultures,the brains are taken from 3-day-old rats, and meninges are removed. Theisolation of cells is achieved by trypsinization (0.25% trypsinsolution, 15 minutes at 37° C.)). After undigested tissue fragments areseparated with the aid of a 40 μm nylon mesh, the isolated cells arecentrifuged off (800 rpm/10 min). The cell pellet is resuspended in theculture medium and moved into 100 ml tissue culture flasks (1brain/tissue culture flask). The cultivation of the cells is carried outover a period of 5-7 days in Dulbeccos modified Eagle Medium (DMEM, withglutamine), supplemented with penicillin (50 U/ml), streptomycin (40μg/ml) and 10% (v/v) fetal calf serum (FCS) at 37° C. and 5% CO₂. Duringthis incubation, an adhesive cellular film is formed, which mainlyconsists of astrocytes. Microglia proliferate as non-adhesive or weaklyadhesive cells on the latter and are harvested via shaking incubation(420 rpm, 1 hour).

To activate the microglia by Aβ-peptide, 2.5×10⁴ microglia/hole aregrown on the Aβ-coated tissue culture plates and incubated over a periodof 7 days in DMEM (with glutamine), supplemented with penicillin (50U/ml), streptomycin (40 μg/ml) and 10% (v/v) fetal calf serum (FCS) at37° C. and 5% CO₂. On day 5, a compound according to the invention isadded at various concentrations (0.1, 0.3, 1.3 and 10 μM).

To quantify the microglia reactivity, the metabolic activity is measuredon cultivation day 7 via the reduction of MTS(3-(4,5-dimethylthiazol-2-yl)-5-(3carboxymethoxyphenyl)-2-(sulfophenyl)-2H-tetrazolium),Owen's reagent, Baltrop, J. A. et al. Bioorg. & Med. Chem. Lett 1, 6111(1991)). The percentage of inhibition relates to a control that istreated only with DMSO. The compounds according to the invention inhibitthe microglia activation.

EXAMPLE 308 Cerebral Brain Infarction in Rats (MCAO Model)

The compounds according to the invention were tested for in vivoactivity in an animal model for cerebral ischemia (stroke), the MCAO(permanent middle cerebral artery occlusion) model. One-sidedobstruction of the middle cerebral artery (MCA) triggers a braininfarction, which is caused by the fact that the corresponding area ofthe brain is undernourished with oxygen and nutrients. The result ofthis undernourishment is a pronounced cellular degeneration and,subsequently, a strong microglia activation. This microglia activationreaches its maximum only after several days, however, and can last forseveral weeks. To test the substances, the compounds according to theinvention were administered intraperitoneally 1-6 days after occlusion.On day 7, the animals were perfused and sacrificed. The extent of themicroglia activation was measured by a modified immunohistochemicalmethod. Vibratom sections of fixed brains were incubated withantibodies, whereby said sections detect the CR3 complement receptor orthe MHCII complex from activated microglia. The quantification of theprimary antibody bond was carried out by an enzyme-coupled detectionsystem. The treatment with the compounds according to the inventionresulted in a significant reduction of microglia activation in the brainhemisphere affected by the brain infarction. The reduction was at least20%.

EXAMPLE 309 Activation of Macrophages

To test substances on macrophages/monocytes, LPS-activated THP-1 cellswere used. For this purpose, 2.5×106 cells/ml in RPMI medium (RPMI1640+10% FCS) were grown. The compounds according to the invention wereadded at a concentration of 5 μM and pre-incubated for 30 minutes. Thestimulation of the cells was carried out overnight at 37 C with 1 μg/mlof LPS. Then, the medium was harvested, and the amount of TNFα wasdetermined quantitatively. The treatment of the cells with thesubstances according to the invention resulted in a reduction of theamount of TNF_(α) of at least 30%.

1. A method of treating inflammation in a patient, comprising administering an effective amount of a benzimidazole compound according to formula I

or a physiologically acceptable salt thereof, in which R¹ means a monocyclic or bicyclic C₆₋₁₂ aryl group or a monocyclic or bicyclic 5- to 10-membered heteroaryl group with 1-4 heteroatoms selected from N, S and O atoms, wherein said aryl or heteroaryl group is optionally substituted with up to three substituents, independently of one another, selected from F, Cl, Br, I, C(NH)NH₂, C(NH)NHR⁴, C(NH)NR⁴R^(4′), C(NR⁴)NH₂, C(NR⁴)NHR^(4′), C(NR⁴)NR⁴R^(4′), XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′)XCN, XCOOH, XCOOR⁴, XCONH₂, XCONR⁴R^(4′), XCONHR⁴, XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XN(SO₂R⁴)SO₂R^(4′), XNR⁴SO₂R^(4′), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, tetrahydro-2,5-dioxopyrrol-1-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, and R⁴, wherein two substituents at R¹, if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl, R² means a monocyclic or bicyclic 5- to 10-membered heteroaryl group with 1-4 heteroatoms selected from N, S and O atoms, wherein said heteroaryl group is optionally substituted with up to three independently of one another, selected from of F, Cl, Br, I, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCOOH, XCOOR⁴, XCONH₂, XCONHR⁴, XCONR⁴R^(4′), XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XN(SO₂R⁴)SO₂R^(4′), XNR⁴SO₂R^(4′), tetrahydro-2,5-dioxopyrrol-1-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, and R⁴,  wherein two substituents at R², if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediyl-bisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl, R³ means one or two substituents, independently of one another, which are hydrogen, F, Cl, Br, I, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCN, XCOOH, XCOOR⁴, XCONH₂, XCONHR⁴, XCONR⁴R^(4′), XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XNR⁴SO₂R^(4′), XN(SO₂R⁴)(SO₂R^(4′)) XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, tetrahydro-2,5-dioxopyrrol-1-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, and/or R⁴,  wherein two substituents at R³, if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl, R⁴ and R^(4′), independently of one another, mean C₁₋₄ perfluoroalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkinyl, C₃₋₇cycloalkyl, (C₁₋₃ alkyl-C₃₋₇cycloalkyl), C₁₋₃ alkyl-C₆₋₁₀ aryl, C₁₋₃ alkyl-5-to-10-membered heteroaryl with 1-4 heteroatoms selected from N, S and O atoms, C₆₋₁₀ aryl, or 5- to 10-membered heteroaryl with 1-4 heteroatoms selected from N, S and O atoms, wherein the aryl and heteroaryl groups are optionally substituted with one or two substituents selected from F, Cl, Br, CH₃, C₂H₅, NO₂, OCH_(3, OC) ₂H₅, CF₃, and C₂F₅, or optionally carry an annelated methanediylbisoxy group or ethane-1,2-diylbisoxy group, and wherein a 5-membered cycloalkyl ring optionally has an N or O ring member, and a 6- or 7-membered cycloalkyl ring optionally has one or two ring members selected from N and O,  wherein ring nitrogens optionally are substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, R⁵ and R^(5′), independently of one another, mean C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆alkinyl (wherein in each case a carbon atom is optionally replaced by O, S, SO, SO₂, NH, NC₁₋₃ alkyl or NC₁₋₃ alkanoyl), C₃₋₇cycloalkyl-C₀₋₃ alkyl, C₆₋₁₀ aryl or 5- to 10-membered heteroaryl with 1-4 heteroatoms selected from N, S, and O atoms, wherein a 5-membered cycloalkyl ring optionally has an N or O ring member and a 6- or 7-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens optionally are substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, wherein the alkyl, alkenyl and alkinyl groups are optionally substituted with one of the previously mentioned cycloalkyls, aryls or heteroaryls, and wherein all previously mentioned alkyl and cycloalkyl radicals are optionally substituted with one or two substituents selected from of CF₃, C₂F₅, OH, OC₁₋₃ alkyl, NH₂, NHC₁₋₃ alkyl, NHC₁₋₃ alkanoyl, N(C₁₋₃ alkyl)₂N(C₁₋₃ alkyl)(C₁₋₃ alkanoyl), COGH, CONH₂, and COOC₁₋₃ alkyl, and all previously mentioned aryl and heteroaryl groups are optionally substituted with one or two substituents selected from of F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅, CF₃, and C₂F₅ or optionally carry an annelated methanediylbisoxy or ethane-1,2-diylbisoxy group, or R⁵ and R^(5′) together with the nitrogen atom form a 5-to 7-membered heterocyclic ring, which optionally contains another oxygen, nitrogen or sulfur atom and is optionally substituted with C₁₋₄ alkyl, C₁₋₄ alkoxy-C₀₋₂ alkyl, C₁₋₄ alkoxycarbonyl, aminocarbonyl or phenyl, A means C₁₋₁₀ alkanediyl, C₂₋₁₀ alkenediyl, C₂₋₁₀ alkinediyl, (C₀₋₅alkanediyl-C₃₋₇, cycloalkanediyl-C₀₋₅ alkanediyl), wherein a 5-membered cycloalkyl ring optionally has a N or O ring member, and a 6-or7-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens are optionally substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, wherein in an aliphatic group, one or two carbon atoms are each optionally replaced by O, NH, NC₁₋₃ alkyl, and/or NC₁₋₃ alkanoyl, and wherein alkyl or cycloalkyl groups are optionally substituted with up to two substituents selected from of ═O, OH, OC₁₋₃ alkyl, NH₂, NHC₁₋₃ alkyl, NHC₁₋₃ alkanoyl, N(C₁₋₃ alkyl)₂, and N(C₁₋₃ alkyl)(C₁₋₃ alkanoyl), B means COOH, COOR⁵, CONH₂, CONHNH₂, CONHR⁵, CONR⁵R^(5′), CONHOH, CONHOR⁵, SO₃H, SO₂NH₂, SO₂NHR⁵, SO₂NR⁵R^(5′), PO³H, PO(OH)(OR⁵), PO(OR⁵)(OR^(5′)), PO(OH)(NHR⁵), PO(NHR⁵)(NHR^(5′)), or tetrazolyl, each bonded to a carbon atom of group A, or the entire group Y-A-B is N(SO₂R⁴)(SO₂R^(4′)) or NHSO₂R⁴, X means a bond, CH₂, (CH₂)₂, CH(CH₃), (CH₂)₃, CH(CH₂CH₃), CH(CH₃)CH₂, or CH₂CH(CH₃), Y means O, NH, NR⁴, NCOR⁴, or NSO₂R⁴, provided that if Y means NH, NR⁴, NCOR⁴ or NSO₂R⁴, and a) R² contains a nitrogen-containing, saturated heterocyclic compound, this heterocyclic compound is not substituted in the imine nitrogen with H, methyl, ethyl, propyl or isopropyl, or b) in optionally present groups XNHR⁴ or XNR⁴R^(4′) of R², R⁴ and/or R^(4′) does not mean C₁₋₄ alkyl, that B does not mean COOH, SO₃H, PO³H₂ or tetrazolyl at the same time R¹ means C₅₋₆ heteroaryl or phenyl which are, independently of one another, unsubstituted or substituted simply with C₁₋₆ alkyl, C₁₋₄ perfluoroalkyl, OC₁₋₆ alkyl, OC₁₋₄ perfluoroalkyl, COOH, COOC₁₋₆ alkyl, COC₁₋₆ alkyl, CONH₂, CONHR⁴, NO₂, NH₂, NHCOR⁴, NHSO₂R⁴, or with 1 or 2 halogen atoms selected from of F, Cl, Br, and I, and R² means C₅₋₆ heteroaryl substituted simply with C₁₋₆ akyl, C₁₋₄ perfluoroalkyl, OC₁₋₆ alkyl, OC₁₋₄ perfluoroalkyl, COOH, COOC₁₋₆ alkyl, COC₁₋₆ alkyl, CONH₂, CONHR⁴, NO₂, NH₂, NHCOR⁴, NHSO₂R⁴, or with 1 or 2 halogen atoms selected from of Cl, Br and I.
 2. A method according to claim 1, wherein R¹ means a monocyclic or bicyclic C₂₋₆ aryl group or a monocyclic or bicyclic 5- to 10-membered heteroaryl group with 1-2 heteroatoms selected from N, S and O atoms, wherein said aryl or heteroaryl group is optionally substituted with up to three substituents, independently of one another, selected from of F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XCN, XCOOH, XCOOR⁴, XCONH₂, XCONR⁴R^(4′), XCONHR⁴, XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, NO₂, XNHR⁴, XNR⁴R^(4′), and R⁴, wherein two substituents at R¹, if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl.
 3. A method according to claim 1, wherein R² means monocyclic or bicyclic 5- to 10-membered heteroaryl group with 1-2 heteroatoms selected from N, S and O atoms, wherein said heteroaryl group is optionally substituted with up to three, independently of one another, selected from of F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCOOH, XCOOR⁴, XCONH₂, XCONHR^(4,)XCONR⁴R^(4′), XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XN(SO₂R⁴)SO₂R^(4′), XNR⁴SO₂R^(4′), and R⁴, wherein two substituents at R², if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl.
 4. A method according to claim 1, wherein R³ means one or two substituents, independently of one another, which are hydrogen, F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCN, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴, XNR⁴N^(4′), XNHSO_(2R) ⁴, XNR⁴SO₂R^(4′), XN(SOR⁴)SOR^(4′), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, and/or R⁴, wherein two substituents at R³, if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl.
 5. A method according to claim 1, wherein R⁴ and R^(4′), independently of one another, mean CF₃, C₂F₅, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkinyl, C₃₋₆ cycloalkyl, (C₁₋₃ alkyl-C₃₋₆ cycloalkyl), phenyl or 5- to 6-membered heteroaryl with 1-2 heteroatoms selected from of N, S and O atoms, wherein the phenyl and heteroaryl groups are optionally, substituted with one or two substituents selected from of F, Cl, Br, CH₃, C₂H₅, OCH_(3, OC) ₂H₅, CF₃, and C₂F₅, and wherein a 5-membered cycloalkyl ring optionally has a N or O ring member, and a 6-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens optionally are substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl.
 6. A method according to claim 1, wherein R⁵ and R^(5′), independently of one another, are optionally C₁₋₆ alkyl (wherein a carbon atom is optionally replaced by O, NH, NC₁₋₃ alkyl, or NC₁₋₃ alkanoyl) or C₃₋₇ cycloalkyl-C₀₋₃-alkyl, wherein a 5- membered cycloalkyl ring optionally has a N or O ring member and a 6- or 7-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens are optionally substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, and wherein the C₁₋₆ alkyl group is optionally substituted with one of the previously mentioned cycloalkyls or a 5- to 6-membered heteroaromatic compound with 1-2 heteroatoms selected from N, S and O atoms, wherein all previously mentioned alkyl and cycloalkyl groups are optionally substituted with up to two substituents selected from of CF₃, OH, and OC₁₋₃ alkyl, and the previously mentioned heteroaryl groups are optionally substituted with one or two substituents selected from of F, Cl, CF₃, CH₃, C₂H₅, OCH₃, and OC₂H₅, or R⁵ and R^(5′) together with the nitrogen atom form a 5- to 7-membered heterocyclic group, which optionally contains another oxygen, nitrogen or sulfur atom and is optionally substituted with C₁₋₄ alkyl, C₁₋₄ alkoxy-C₀₋₂ alkyl, C₁₋₄ alkoxy-carbonyl, aminocarbonyl or phenyl.
 7. A method according to claim 1, wherein A means C₁₋₁₀ alkanediyl, C₂₋₁₀ alkenediyl, C₂₋₁₀ alkinediyl, (C₀₅ alkanediyl-C₃₋₇ cycloalkanediyl-C₀₋₅ alkanediyl), wherein a 5-membered cycloalkyl ring optionally has a N or O ring member and a 6- or 7-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens are optionally substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, wherein in an aliphatic group one or two carbon atoms are each optionally replaced by O, NH, N C₁₋₃ alkyl, and/or NC₁₋₃ alkanoyl.
 8. A method according to claim 1, wherein B means COOH, COOR⁵, CONH₂, CONHR⁵, CONR⁵R^(5′), CONHOH, CONHOR⁵ or tetrazolyl, in each case bonded to a carbon atom of group A.
 9. A method according to claim 1, wherein X means a bond or CH₂.
 10. A method according to claim 1, wherein Y means O.
 11. A method according to claim 1, wherein the compound administered is 6-[[1-phenyl-2-(4-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester.
 12. A method according to claim 1, wherein the compound administered is 6-[[1-phenyl-2-(benzothien-2-yl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, 6-[[1-phenyl-2-(benzothien-2-yl)-1H-benzimidazol-6-yl]oxy]hexanoic acid, 6-[[1-phenyl-2-(3-pyridinyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, 6-[[1-(4-methylphenyl)-2-(3-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, 6-[[1-(4-methylphenyl)-2-(4-pyridyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, 6-[[1-(4-methylphenyl)-2-(2-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, 6-[[1-(4-methylphenyl)-2-(3-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, 6-[[2-(3-indolyl)-1-(4-methylphenyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, 6-[[1-(4-methylphenyl)-2-(2-furyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, 6-[[1-(4-methylphenyl)-2-(3-furyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, 6-[[1-(4-methylphenyl)-2-(5-methyl-2-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester, or 6-[[1-(4-methylphenyl)-2-(3-methyl-2-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester.
 13. A method for treating a patient suffering from chronic inflammation comprising administering to said patient an effective amount of a benzimidazole compound of formula II

or a physiologically compatible acceptable salt thereof, in which R¹ means a monocyclic or bicyclic C₆₋₁₂ aryl group or a monocyclic or bicyclic 5- to 10-membered heteroaryl group with 1-4 heteroatoms selected from N, S and O atoms, wherein said aryl or heteroaryl group is optionally substituted with up to three substituents, independently of one another, selected from F, Cl, Br, I, C(NH)NH₂, C(NH)NHR⁴, C(NH)NR⁴R^(4′), C(NR⁴)NH₂, C(NR⁴)NHR^(4′), C(NR⁴)NR⁴R^(4′), XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′) XCN, XCOOH, XCOOR⁴, XCONH₂, XCONR⁴R^(4′), XCONHR⁴, XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, S O₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XN(SO₂R⁴)(SO₂R^(4′)), XNR⁴SO₂R^(4′), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, tetrahydro-2,5-dioxopyrrol-1-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, and R⁴, wherein two substituents at R¹, if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl, R² means a monocyclic or bicyclic 5- to 10-membered heteroaryl group with 1-4 heteroatoms selected from N, S and O atoms, wherein said heteroaryl group is optionally substituted with up to three substituents, independently of one another, selected from of F, Cl, Br, I, C(NH)NH₂, C(NH)NHR⁴, C(NH)NR⁴R^(4′), C(NR⁴)NH₂, C(NR⁴)NHR^(4′), C(NR⁴)NR⁴R^(4′), XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCN, XCOOH, XCOOR⁴, XCONH₂, XCONR⁴R^(4′), XCONHR⁴, XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴, XNR⁴R^(4′)XNHSO₂R^(4, XN(SO) ₂R⁴)(SO₂R^(4′)), XNR⁴SO₂R^(4′), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, tetrahydro-2,5-dioxopyrrol-1-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, and R⁴, wherein two substituents at R², if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediyl-bisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl, R³ stands for one or two substituents, independently of one another, which are hydrogen, F, Cl, Br, I, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCN, XCOOH, XCOOR⁴, XCONH₂, XCONHR⁴, XCONR⁴R^(4′), XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XNR⁴SO₂R^(4′), XN(SO₂R⁴)(SO₂R^(4′)), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, tetrahydro-2,5-dioxopyrrol-i-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, or R⁴, two substituents at R³, if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl, R⁴ and R^(4′), independently of one another, mean C₁₋₄ perfluoroalkyl, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆alkinyl, C₃₋₇cycloalkyl, (C₁₋₃ alkyl-C₃₋₇cycloalkyl), C₁₋₃ alkyl-C₆₋₁₀ aryl, C₁₋₃ alkyl-5-to-10-membered heteroaryl with 1-4 heteroatoms selected from N, S and O atoms, C₆₋₁₀ aryl, or 5- to 10-membered heteroaryl with 1-4 heteroatoms selected from N, S and O atoms, wherein the C₆₋₁₀ aryl and heteroaryl groups are optionally substituted with one or two substituents selected from F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅, CF₃, and C₂F₅ or optionally carry an annelated methanediylbisoxy group or ethane-1,2-diylbisoxy group, and wherein a 5-membered cycloalkyl ring optionally has a N or O ring member, and a 6- or 7-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens are optionally substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, R⁵ and R^(5′), independently of one another, mean hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆alkinyl, (wherein in each case a carbon atom is optionally replaced by O, S, SO, SO₂, NH, N C₁₋₃ alkyl or N C₁₋₃ alkanoyl), C₃₋₇ cycloalkyl-C₀₋₃ alkyl, (wherein a 5-membered cycloalkyl ring optionally has a N or O ring member, and a 6- or 7-membered cycloalkyl ring optionally has one or two ring members selected from N and O, and wherein ring nitrogens are optionally substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl), C₆₋₁₀ aryl or 5- to 10-membered heteroaryl with 1-4 heteroatoms selected from N, S, and O atoms, wherein the mentioned alkyl, alkenyl and alkinyl groups are optionally substituted with one of the previously mentioned cycloalkyls, aryls or heteroaryls, wherein all previously mentioned alkyl and cycloalkyl radicals are optionally substituted with up to two substituents selected from CF₃, C₂F₅, OH, OC₁₋₃ alkyl, NH₂, NHC₁₋₃ alkyl, NHC₁₋₃ alkanoyl, N(C₁₋₃ alkyl)₂, N(C₁₋₃ alkyl)(C₁₋₃ alkanoyl), COOH, CONH₂, and COOC₁₋₃ alkyl, and all previously mentioned aryl and heteroaryl groups are optionally substituted with one or two substituents selected from F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅, CF₃, and C₂F₅ or optionally carry an annelated methanediylbisoxy or ethane-1 ,2-diylbisoxy group, or R⁵ and R^(5′) together with the nitrogen atom form a 5-to 7-membered heterocyclic group, which optionally contains another oxygen, nitrogen or sulfur atom and is optionally substituted with C₁₋₄ alkyl, C₁₋₄ alkoxy-C₀₋₂ alkyl, C₁₋₄ alkoxy-carbonyl, aminocarbonyl or phenyl, A means C₁₋₁₀ alkanediyl, C₂₋₁₀ alkenediyl, C₂₋₁₀ alkinediyl, (C₀₋₅ alkanediyl-C₃₋₇ cycloalkanediyl-C₀₋₅ alkanediyl), (C₀₋₅ alkanediylarylene-C₀₋₅ alkanediyl), or C₀₋₅ alkanediyl-heteroarylene-C₀₋₅ alkanediyl), wherein the aryl and heteroaryl groups are optionally substituted with one or two substituents selected from F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅, CF₃, and C₂F₅, wherein a 5-membered cycloalkyl ring optionally has a N or O ring member and a 6- or 7-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens are optionally substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, wherein in an aliphatic group one or two carbon atoms are each optionally replaced by O, NH, NR⁴, NCOR⁴, or NSO₂R⁴, and wherein alkyl or cycloalkyl groups are optionally substituted with up to two substituents selected from F, OH, OR⁴, OCOR^(4, ═O, NH) ₂, NR⁴R^(4′), NHCOR⁴, NHCOOR⁴, NHCONHR⁴, NHSO₂R⁴SH, and SR⁴, B means hydrogen, OH, OCOR⁵, OCONHR⁵, OCOOR⁵, COR⁵, C(NOH)R⁵, C(NOR⁵)R⁵′, C(NO(COR⁵))R⁵′, COOH, COOR⁵, CONH₂, CONHNH₂, CONHR⁵, CONR⁵R⁵′, CONHOH, CONHOR⁵, SO₃H, SO₂NH₂, SO₂NHR⁵, SO₂NR⁵R⁵′, PO₃H, PO(OH)(OR⁵), PO(OR⁵)(OR⁵′), PO(OH)(NHR⁵), PO(NHR⁵)(NH R⁵′), or tetrazolyl, each bonded to a carbon atom of group A, or the entire group Y-A-B is N(SO₂R⁴)(SO₂R^(4′)) or NHSO₂R⁴, X means a bond, CH₂, (CH₂)₂, CH(CH₃), (CH₂)₃, CH(CH₂CH₃), CH(CH₃)CH₂, or CH₂CH(CH₃), and Y means a bond, O, S, SO, SO₂, NH, NR⁴, NCOR⁴, or NSO₂R⁴.
 14. A method according to claim 13, wherein R¹ means a monocyclic or bicyclic aryl group or a monocyclic or bicyclic 5- to 10-membered heteroaryl group with 1-2 heteroatoms selected from N, S and O atoms, wherein said aryl or heteroaryl group is optionally substituted with up to three substituents, independently of one another, selected from of F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XCN, XCOOH, XCOOR⁴, XCONH₂, XCONR⁴R^(4′), XCONHR⁴, XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, NO₂, XNHR⁴, XNR⁴R^(4′), and R⁴, wherein two substituents at R¹, if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl.
 15. A method according to claim 13, wherein R² means a monocyclic or bicyclic 5- to 10-membered heteroaryl group with 1-2 heteroatoms selected from N, S and O atoms, wherein the heteroaryl group is optionally substituted with up to three, independently of one another, selected from of F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCN, XCOOH, XCOOR⁴, XCONH₂, XCONR⁴R^(4′), XCONHR⁴, XCONHOH, XCONHOR⁴, XCOSR⁴, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴, XNR^(4R) ^(4′), XNHSO₂R⁴, XN(SO₂R⁴)(SO₂R^(4′)), XNR⁴SO₂R^(4′), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, and R⁴, wherein two substituents at R², if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl.
 16. A method according to claim 13, wherein R³ stands for one or two substituents, independently of one another, selected from which are hydrogen, F, Cl, Br, XOH, XOR⁴, XOCOR⁴, XOCONHR⁴, XOCOOR⁴, XCOR⁴, XC(NOH)R⁴, XC(NOR⁴)R^(4′), XC(NO(COR⁴))R^(4′), XCN, XSR⁴, XSOR⁴, XSO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂NR⁴R^(4′), NO₂, XNH₂, XNHR⁴, XNR⁴R^(4′), XNHSO₂R⁴, XNR⁴SO₂R^(4′), XN(SO₂R⁴)(SO₂R^(4′)), XNHCOR⁴, XNHCOOR⁴, XNHCONHR⁴, and R⁴, wherein two substituents at R³, if they are in ortho-position to one another, are optionally linked to one another to jointly form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, or butane-1,4-diyl.
 17. A method according to claim 13, wherein R⁴ and R^(4′), independently of one another, mean CF₃, C₂F₅, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkinyl, C₃₋₆ cycloalkyl, (C₁₋₃ alkyl-C₃₋₆ cycloalkyl), C₁₋₃ alkylaryl, C₁₋₃ alkylheteroaryl, monocyclic aryl or 5- to 6-membered heteroaryl with 1-2 heteroatoms selected from N, S and O atoms, wherein the aryl and heteroaryl groups are optionally substituted with one or two substituents selected from of F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅, CF₃, and C₂F₅ or optionally carry an annelated methanediylbisoxy or ethane-1,2-diylbisoxy group, and wherein a 5-membered cycloalkyl ring optionally has a N or O ring member, and a 6-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens are optionally substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl.
 18. A method according to claim 13, wherein R⁵ and R^(5′), independently of one another, are optionally C₁₋₆ alkyl (wherein a carbon atom is optionally replaced by O, NH, NC₁₋₃ alkyl, or NC₁₋₃ alkanoyl), or C₃₋₇cycloalkyl-C₀₋₃ alkyl (wherein a 5- membered cycloalkyl ring optionally has a N or O ring member, and a 6- or 7-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens are optionally substituted with C₁₋₃alkyl or C₁₋₃ alkanoyl), wherein the mentioned C₁₋₆ alkyl is optionally substituted with one of the previously mentioned cycloalkyls or a 5- to 6-membered heteroaromatic compound with 1-2 heteroatoms selected from N, S and O atoms, and wherein all previously mentioned alkyl and cycloalkyl groups are optionally substituted with up to two substituents selected from of CF₃, OH, and OC₁₋₃ alkyl, and the previously mentioned heteroaryl groups are optionally substituted with one or two of F, Cl, CF₃, CH₃, C₂H₅, OCH₃, and/or OC₂H₅, or R⁵ and R^(5′) together with the nitrogen atom form a 5- to 7-membered heterocyclic group, which optionally contains another oxygen, nitrogen or sulfur atom and is optionally substituted with C₁₋₄ alkyl, C₁₋₄ alkoxy-C₀₋₂ alkyl, C₁₋₄ alkoxy-carbonyl, aminocarbonyl or phenyl.
 19. A method according to claim 13, wherein A means C₁₋₁₀ alkanediyl, C₂₋₁₀ alkenediyl, C₂₋₁₀ alkinediyl, (C₀₋₅ alkanediyl-C₃₋₇ cycloalkanediyl-C₀₋₅ alkanediyl), or (C₀₋₅ alkanediyl-heteroarylene-C₀₋₅ alkanediyl), wherein when a heteroaryl group is present it is optionally substituted with one or two substituents selected from of F, Cl, Br, CH₃, C₂H₅, NO₂, OCH₃, OC₂H₅, CF₃, and C₂F₅, and wherein a 5-membered cycloalkyl ring optionally has a N or O ring member, and a 6- or 7-membered cycloalkyl ring optionally has one or two ring members selected from N and O, wherein ring nitrogens are optionally substituted with C₁₋₃ alkyl or C₁₋₃ alkanoyl, wherein in an aliphatic group one or two carbon atoms are optionally replaced by O, NH, NC₁₋₃ alkyl, NC₁₋₃ alkanoyl, and/or NSO₂C₁₋₃ alkyl, and wherein alkyl or cycloalkyl groups are optionally substituted with up to two F atoms or by one of OH, OC₁₋₃ alkyl, OC₁₋₃ alkanoyl, ═O, NH₂, NHC₁₋₃ alkyl, N(C₁₋₃ alkyl)₂, NHC₁₋₃ alkanoyl, N(C₁₋₃ alkyl)(C₁₋₃ alkanoyl), NHCOOC₁₋₃ alkyl, NHCONHC₁₋₃ alkyl, NHSO_(2C) ₁₋₃ alkyl, SH or SC₁₋₃ alkyl.
 20. A method according to claim 13, wherein B means hydrogen, OH, OCOR⁵, OCONHR⁵, OCOOR⁵, COOH, COOR⁵, CONH₂, CONHR⁵, CONR⁵R^(5′), CONHOH, CONHOR⁵, or tetrazolyl, in each case bonded to a carbon atom of group A.
 21. A method according to claim 13, wherein X means a bond or CH₂.
 22. A method according to claim 13, wherein Y means a bond, O, S, NH, NR⁴, NCOR⁴ or NSO₂R⁴.
 23. A method according to claim 1, wherein the compound administered is 6-[[1-phenyl-2-(benzothien-2-yl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester.
 24. A method according to claim 13, wherein the compound administered is 6-[[1-phenyl-2-(benzothien-2-yl)-1H-benzimidazol-6-yl]oxy]hexanoic acid methyl ester.
 25. A method according to claim 23, wherein the patient suffers from Alzheimer's disease, AIDS dementia or stroke.
 26. A method according to claim 24, wherein the patient suffers from Alzheimer's disease, AIDS dementia or stroke.
 27. A method according to claim 1, wherein the patient suffers from AIDS dementia, amyotrophic lateral sclerosis, Creutzfeldt-Jacob disease, Down's syndrome, diffuse Lewy body's disease, Huntington's disease, leukoencephalopathy, multiple sclerosis, Parkinson's disease, Pick's disease, Alzheimer's disease, stroke, temporary lobe epilepsy or a tumor.
 28. A method according to claim 13, wherein the patient suffers from AIDS dementia, amyotrophic lateral sclerosis, Creutzfeldt-Jacob disease, Down's syndrome, diffuse Lewy body's disease, Huntington's disease, leukoencephalopathy, multiple sclerosis, Parkinson's disease, Pick's disease, Alzheimer's disease, stroke, temporary lobe epilepsy or a tumor.
 29. A method according to claim 1, wherein the patient suffers from Alzheimer's disease, AIDS dementia or stroke.
 30. A method according to claim 13, wherein the patient suffers from Alzheimer's disease, AIDS dementia or stroke.
 31. A method according to claim 1, wherein the inflammation is associated with microglia activation.
 32. A method according to claim 13, wherein the inflammation is associated with microglia activation. 